| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In both promoters , the binding site of Pax 8 overlaps with that of TTF 1 , a homeodomain containing protein involved in the activation of thyroid specific transcription . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| TTF 1 and Pax 8 are thyroid specific transcription factors , from homeo and paired box genes , respectively , that are responsible for thyroid development and for thyroglobulin and thyroperoxidase gene expression . ^^^ However , TTF 1 and Pax 8 preferentially bind to the thyroglobulin and thyroperoxidase promoters , respectively . ^^^ Moreover , these data suggest that TTF 1 and Pax 8 would be differentially regulating thyroglobulin and thyroperoxidase gene transcription . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Differentially regulated expression of the TSHR and TG by cAMP and insulin depend on differences in the specificity of the TTF 1 site , that is , the lack of Pax 8 interactions with the TSHR , and the IRE sites . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Sequence analysis identifies a potential TTF 1 site at 878 bp ; deoxyribonuclease 1 footprinting shows that the 881 to 866 bp region is protected by recombinant TTF 1 protein and by nuclear extracts from FRTL 5 thyroid cells that contain TTF 1 , but not by extracts from nonfunctioning FRT thyroid or Buffalo rat liver ( BRL ) cells , which have no TTF 1 , or by Pax 8 . ^^^ Like the down stream TSHR TTF 1 binding site , the up stream TTF 1 site is different from TTF 1 sites in the thyroglobulin and thyroid peroxidase promoter , in that it does not interact with Pax 8 . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Expression of thyroid specific transcription factors TTF 1 and PAX 8 in human thyroid neoplasms . ^^^ TTF 1 and PAX 8 are tissue specific transcription factors expressed in the thyroid follicular cells , contributing to the maintenance of the differentiated phenotype . ^^^ In fact , it has been demonstrated that TTF 1 and PAX 8 are able to activate transcription from thyroglobulin and thyroperoxidase ( TPO ) promoters , the transcriptional activity of which is in vivo restricted only to the thyroid follicular cell . ^^^ In order to gain insight into how these transcription factors control in vivo the differentiation of the thyroid cell and to have a better molecular characterization of human thyroid tumors , TTF 1 , PAX 8 , thyroglobulin , and TPO mRNA levels were measured in nonmalignant and malignant human thyroid tissues . ^^^ Results indicate that the expression of TTF 1 and PAX 8 is not sufficient per se for the expression of the thyroid differentiated phenotype . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Redox regulation of thyroid transcription factors , Pax 8 and TTF 1 , is involved in their increased DNA binding activities by thyrotropin in rat thyroid FRTL 5 cells . ^^^ Thyroid enriched transcription factors , Pax 8 and TTF 1 , are involved in the thyroid specific expression of thyroglobulin ( TG ) gene . ^^^ These observations indicate that reduction is required for full DNA binding of Pax 8 and TTF 1 in vitro . ^^^ Pax 8 and TTF 1 binding activities were gradually increased during the initial 6 h after TSH . ^^^ These results suggest that TSH up regulates the binding of Pax 8 and TTF 1 , at least in part , by reducing the preexisting , oxidized forms in FRTL 5 cells . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The possible involvement of thyroid transcription factors , TTF 1 , TTF 2 and Pax 8 , in the induction of TG gene transcription was studied using an electrophoretic mobility shift assay . ^^^ It was demonstrated that TSH , insulin or serum increased not only TTF 2 binding activity but also the binding activities of TTF 1 and Pax 8 . ^^^ However , the magnitude of the increase in TTF 1 and Pax 8 mRNA levels per unit of DNA was less than that of the binding activity . ^^^ Taken together , our results suggest that TSH , insulin and serum increase the binding activities of TTF 1 and Pax 8 to the TG promoter presumably through the posttranslational modification of the factors , thereby enhancing TG gene transcription . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Disrupted co ordination of Pax 8 and thyroid transcription factor 1 gene expression in a dedifferentiated rat thyroid tumour cell line derived from FRTL 5 . ^^^ To investigate the role of the transcription factors Pax 8 and thyroid transcription factor 1 ( TTF 1 ) in rat thyroid tumorigenesis , RNA expression of these two thyroid specific nuclear factors was measured in FRTL 5 / TA tumour cells and compared with the expression in wild type FRTL 5 cells . ^^^ These data indicated that the loss of thyroid specific expression of Tg and TPO genes in FRTL 5 / TA cells was not related to changes in TTF 1 gene expression but rather to reduced Pax 8 gene expression . ^^^ It was concluded that a disruption of the co ordinated expression of TTF 1 and Pax 8 is implicated in the loss of thyroid phenotype of FRTL 5 / TA cells in terms of reduced Tg and TPO expression . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Results were related to clinical parameters , transcript levels of thyroglobulin ( TG ) , and thyroid peroxidase ( TPO ) , as well as transcript levels of thyroid transcription factor 1 ( TTF 1 ) which regulates the expression of all three genes and paired box gene 8 ( Pax 8 ) which regulates TG and TPO gene expression . ^^^ Pax 8 and TTF 1 transcripts were detectable in normal thyroids ; however , Pax 8 expression was increased in Graves ' thyroids ( 3 . 8 fold ) , whereas TTF 1 expression was only minimally changed in all thyroids investigated . ^^^ Pax 8 expression correlated with TG and TPO expression ( in all cases , p = 0 . 0001 ) ; TTF 1 , despite its minimal change , still correlated with TG ( p = 0 . 0471 ) but not with TPO expression ( p = 0 . 0984 ) . ^^^ TTF 1 , again despite its minimal changes , correlated positively with TSH R gene expression ( p = 0 . 0251 ) ; however , surprisingly , Pax 8 , which does not regulate TSH R gene expression , correlated even better with TSH R transcript levels ( p = 0 . 0001 ) . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Two transcription factors , TTF 1 and Pax 8 , have been implicated in transcriptional activation of Tg and TPO , even though the onset of their expression is at E9 . 5 , suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| TSH / cAMP induced silencer activity is associated with the formation of novel complexes with the 38 base pair silencer , whose appearance requires the CRE and involves ubiquitous and thyroid specific proteins as follows : the CRE binding protein , a Y box protein termed thyrotropin receptor ( TSHR ) suppressor element protein 1 ( TSEP 1 ) ; thyroid transcription factor 1 ( TTF 1 ) ; and Pax 8 . ^^^ TTF 1 is an enhancer of class 1 promoter activity ; Pax 8 and TSEP 1 are suppressors . ^^^ TSH / cAMP decreases TTF 1 complex formation with the silencer , thereby decreasing maximal class 1 expression ; TSH / cAMP enhance TSEP 1 and Pax 8 complex formation in association with their repressive actions . ^^^ TSEP 1 , TTF 1 , and / or Pax 8 are involved in TSH / cAMP induced negative regulation of the TSH receptor gene in thyrocytes , suppression of MHC class 2 , and up regulation of thyroglobulin . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Northern gel analysis revealed that all of these cell lines expressed Pax 8 messenger ribonucleic acid ; additionally , only BHP 18 21 cells expressed TTF 1 messenger ribonucleic acid . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The expression of two other tissue specific proteins , thyroid transcription factor 1 and Pax 8 , was unchanged . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Two transcription factors , TTF 1 and Pax 8 , have been implicated in thyroid specific expression of the thyroglobulin gene . ^^^ FRT cells contain Pax 8 but they lack TTF 1 . ^^^ Since transfection of TTF 1 expression vectors in non thyroid cell types did not result in thyroglobulin gene expression , it is suggested that Pax 8 , in addition , perhaps , to a specific cellular environment , might be required for thyroid specific expression of the thyroglobulin gene . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Conversely , PAX 8 and thyroid transcription factor 1 , whose expression is thyroid specific , was kept in an FB 1 cell line at a level comparable with that observed in normal thyroid tissue . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Expression of the RET / PTC1 oncogene impairs the activity of TTF 1 and Pax 8 thyroid transcription factors . ^^^ Specific transcription factors , namely , TTF 1 and Pax 8 , regulate the expression of differentiated functions in thyroid cells . ^^^ We conclude that the RET / PTC1 oncogene alters the expression of the thyroid differentiated phenotype by at least two different mechanisms , ie . , down regulation of Pax 8 protein and mRNA expression and impaired function of TTF 1 and Pax 8 , which occurs at a posttranslational level . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The TSH increased nuclear factor in FRTL 5 cells interacting with the NIS TRE is distinct from TTF 1 , thyroid transcription factor 2 , or Pax 8 , as evidenced by the absence of competition using oligonucleotides specific for these factors in gel shift assays . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Major histocompatibility complex class 1 gene expression , which also is regulated by TTF 1 and Pax 8 in the thyroid , is decreased simultaneously . ^^^ In this report we show that follicular TG counter regulates TSH increased , thyroid specific gene transcription by suppressing expression of the TTF 1 , TTF 2 , and Pax 8 genes . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Gel retardation assays suggest that the mechanism by which the Pax 8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF 1 for a common binding site . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Overexpression of TTF 1 and PAX 8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines . ^^^ The inhibition of both Tg and thyroid specific transcription factor ( TTF 1 and PAX 8 ) gene expression , however , has been well documented in thyroid carcinomas . ^^^ We therefore examined the effects of overexpression of TTF 1 and PAX 8 on Tg gene promoter activity in the human thyroid carcinoma cell lines , ARO ( anaplastic ) and WRO ( follicular ) . ^^^ Tg , TTF 1 , and PAX 8 gene expression were also examined by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ RESULTS : ARO and WRO exhibited decreased gene expression of Tg , TTF 1 , and PAX 8 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In addition , in view of the recent identification of putative binding sites for the transcription factors thyroid transcription factor 1 ( TTF 1 ) and human paired box protein 8 ( Pax 8 ) in the human NIS gene promoter , we used reverse transcriptase polymerase chain reaction ( RT PCR ) to assess in these same samples the levels of TTF 1 and Pax 8 gene expression . ^^^ Immunohistochemical analysis revealed abundant hNIS protein expression by thyroid follicular cells in GD , moderate and heterogeneous levels in NMNG , and very low levels in CBTN . hNIS mRNA levels were correlated with TTF 1 and Pax 8 gene expression in GD and , to a lesser degree , in AFTN , NMNG , and IDG , but not in CBTN . ^^^ In general , hNIS gene expression was more closely correlated with TTF 1 as compared to Pax 8 gene expression . ^^^ In addition to TTF 1 and Pax 8 , other transcription factors and enhancer elements may contribute to regulation of NIS gene promoter activity . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Major histocompatibility complex ( MHC ) class 1 gene expression , which is also regulated by TTF 1 and Pax 8 in the thyroid , is simultaneously decreased ; this maintains self tolerance in the face of TSH increased gene products necessary for thyroid hormone formation . ^^^ We now show that follicular TG , 27S > 19S > 12S , counter regulates TSH increased thyroid specific gene transcription by suppressing the expression of the TTF 1 , TTF 2 , and Pax 8 genes . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Proteins including thyroid transcription factors 1 ( TTF 1 ; refs 4 , 5 ) and 2 ( TTF 2 ; refs 6 , 7 ) and Pax 8 ( refs 8 , 9 ) are abundant in the developing mouse thyroid and are known to regulate genes expressed during its differentiation ( for example , thyroid peroxidase and thyroglobulin genes ) . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Thyroid specific transcription factors TTF 1 and Pax 8 play a decisive role in the determination and maintenance of cellular phenotype activating thyroglobulin ( Tg ) , thyroperoxidase ( TPO ) , thyrotropin receptor ( TSH R ) and the sodium / iodide symporter ( NIS ) gene transcription . ^^^ In the present work , we have studied the expression of TTF 1 and Pax 8 and their target genes in samples derived from thyroid neoplasms of follicular origin , as well as in medullary carcinoma ( MTC ) , obtained from surgery or from fine needle aspiration ( FNA ) biopsies . ^^^ The results show that TTF 1 and Pax 8 are expressed in well differentiated adenomas and that their expression decreases in less differentiated papillary and follicular carcinomas and is lost in undifferentiated anaplastic carcinomas . ^^^ Cotransfection with expression vectors for TTF 1 and Pax 8 resulted in the stimulation of transcription to a different extent for each promoter . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Tumor necrosis factor alpha regulation of thyroid transcription factor 1 and Pax 8 in rat thyroid FRTL 5 cells . ^^^ In the present study , we show that TNF alpha suppresses DNA binding activity of thyroid transcription factors , Pax 8 and thyroid transcription factor 1 ( TTF 1 ) , which is , in part , involved in TNF alpha induced decrease in TG gene expression . ^^^ In gel mobility shift analyses , protein DNA complexes formed by TTF 1 and Pax 8 were reduced when the nuclear extracts prepared from TNF alpha treated FRTL 5 cells were used . ^^^ Mutation of the TTF 1 / Pax 8 binding site lost the TNF alpha induced decrease in TG promoter activity in a transfection experiment . ^^^ These results indicate that TNF alpha suppresses the activity of TTF 1 and Pax 8 by different mechanisms , which , in part , seem to be involved in TNF alpha induced decrease in TG gene expression . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Most permanent cases ( 80 85 % ) result from alterations in the formation of the thyroid gland during embryogenesis ( thyroid dysgenesis ) , and several were shown recently to be produced by mutations in genes responsible for the development of thyroid follicular cells ( TITF 1 , TITF 2 , PAX 8 and TSHR ) . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| As both Tg and TPO promoters depend upon the thyroid specific transcription factors , thyroid specific transcription factor 1 ( TTF 1 ) and Pax 8 for full transcriptional activity , we tested whether reduction of GSH concentration impairs the activity of these transcription factors . ^^^ After BSO treatment of FRTL 5 cells , both transcription factors fail to trans activate the respective chimerical targets , C 5 and B cell specific activating protein promoters , containing , respectively , multimerized TTF 1 or Pax 8 binding sites only as well as the Tg and TPO natural promoters . ^^^ Furthermore , the Pax 8 mRNA steady state concentration does not change in BSO treated cells , whereas TTF 1 mRNA slightly decreases . ^^^ Immunoblotting analysis of FRTL 5 nuclear extracts does not show significant modification of the Pax 8 concentration in BSO treated cells , whereas a decrease of 25 % in TTF 1 protein is revealed . ^^^ Finally , different mechanisms seem to act on TTF 1 and Pax 8 functional impairment in BSO treated cells . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Role of insulin and serum on thyrotropin regulation of thyroid transcription factor 1 and pax 8 genes expression in FRTL 5 thyroid cells . ^^^ Moreover , this increase is paralleled by an increase in Pax 8 protein binding to an oligonucleotide derived from the C site of the Tg promoter , which can bind both TTF 1 and Pax 8 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| To correlate the differentiation phenotype of two human thyroid cancer cell lines with their expression of various molecular markers , we analyzed the mRNA levels of four thyroid specific genes , including thyrotropin receptor ( TSHR ) , thyroglobulin ( Tg ) , thyroid transcription factor 1 ( TTF 1 ) , and paired box containing transcription factor 8 ( PAX 8 ) genes . ^^^ The results showed a differentiation status related pattern in which a well differentiated cell line ( WRO ) expressed all the four genes , in contrast to an anaplastic cell line ( ARO ) that expressed TTF 1 and reduced levels of TSHR , but no Tg or PAX 8 genes . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| By using co transfection assays we demonstrate that Hex is a repressor of the thyroglobulin promoter and that it is able to abolish the activating effects of both TTF 1 and Pax 8 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In this paper , we demonstrate that TTF 2 is able to inhibit the activity of the thyroid specific transcription factors TTF 1 and Pax 8 only on certain promoters . ^^^ We suggest that TTF 2 is able to interfere with a specific cofactor required for TTF 1 and Pax 8 activity . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Messenger ribonucleic acid ( mRNA ) expression of thyroid transcription factor 1 and PAX 8 was also detected . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Altered expression of the thyroid transcription factors Pax 8 , TTF 1 , and TTF 2 was also observed . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| A set of transcriptional regulators , unique to the thyroid follicular cell type , has been identified as responsible for thyroid specific gene expression ; it comprises three transcription factors , named TTF 1 , TTF 2 , and Pax 8 , each of which is expressed also in cell types different from the thyroid follicular cells . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Among the transcription factors involved in the regulation of these genes , TTF 1 and TTF 2 were still detected at nearly wild type levels , while a specific loss of the paired domain transcription factor Pax 8 was observed . ^^^ Moreover , we show that Pax 8 and TTF 1 cooperate in the activation of the thyroglobulin promoter and that additional thyroid specific mechanism ( s ) are involved in such a cooperation . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In both cases , expression of RAS at a level sufficient to induce rapid proliferation did not lead to loss of differentiation as shown by expression of cytokeratin 18 , E cadherin , thyroglobulin , TTF 1 and Pax 8 proteins . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| When the nuclear extracts prepared from TGF beta 1 treated FRTL 5 cells were used in gel mobility shift assays , the amount of protein DNA complex formed by Pax 8 was reduced , both in the presence and in the absence of TSH , but protein DNA complexes formed by thyroid transcription factor 1 ( TTF 1 ) and TTF 2 were not . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Highly specialized cells , the thyrocytes , express a thyroid specific set of genes for thyroglobulin ( Tg ) , thyroperoxidase , and the transcription factors TTF 1 , TTF 2 , and Pax 8 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Three genes , TTF 1 , TTF 2 , and PAX 8 , involved in thyroid gland development and migration have been identified . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The synergistic activity of thyroid transcription factor 1 and Pax 8 relies on the promoter / enhancer interplay . ^^^ The transcription factors , thyroid transcription factor 1 ( TTF 1 ) and Pax 8 , play a pivotal role in the transcriptional regulation of the thyroid differentiation marker genes and in the differentiation of the thyroid follicular cells . ^^^ Here we show that TTF 1 and Pax 8 cooperatively activate their target genes and that their synergistic activity requires the cross talk between enhancer and gene promoter . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| To understand the molecular regulation of these genes in thyroid cells , the effect of thyroid transcription factor 1 ( TTF 1 ) and the paired domain containing protein 8 ( Pax 8 ) on the transcriptional activity of the deiodinase promoters were studied . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Thyroid transcription factor 1 and Pax 8 synergistically activate the promoter of the human thyroglobulin gene . ^^^ To obtain new insights in the regulation of Tg gene expression , we investigated the interaction of the human Tg promoter with the thyroid specific transcription factors TTF 1 and Pax 8 . ^^^ A reporter gene , containing a 202 bp fragment from the human Tg 5 ' flanking region including the promoter sequence and the transcriptional start site , and expression vectors containing the cDNAs for human TTF 1 and Pax 8 were used in cotransfection experiments , in the non thyroidal cell lines COS 7 and HeLa . ^^^ Pax 8 increased the specific transcriptional activity of the Tg promoter about threefold , whereas cotransfection with the homeodomain containing protein TTF 1 stimulated promoter activity from six to tenfold . ^^^ The present results demonstrate that the activity of the human Tg promoter is closely dependent on the function of TTF 1 and Pax 8 , opening the field for further investigations of pathological alterations of Tg gene expression . . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Transcriptional regulation of the human sodium / iodide symporter gene by Pax 8 and TTF 1 . ^^^ We investigated the influence of the thyroid specific transcription factors TTF 1 and Pax 8 on the NIS promoter and its 5 ' flanking sequence . ^^^ Reporter genes containing the corresponding genomic fragments coupled to a luciferase reporter gene were cotransfected with expression vectors carrying the the cDNA ' s for TTF 1 and Pax 8 . ^^^ A putative NIS upstream enhancer ( NUE ) 9000 bp upstream of the NIS gene , which was cloned based on its sequence homology to the rat NUE , was not transactivated by either Pax 8 or TTF 1 . ^^^ The present data demonstrate , that the combination of Pax 8 and TTF 1 is less important for NIS gene transcription than for other thyroid specific genes . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The molecular defects known to date only explain a minority of these cases and include mutations in the paired box transcription factor PAX 8 , and the thyroid transcription factors TTF 1 and TTF 2 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Recent studies reported that mutations involving Thyroid Transcriptor Factors ( TTF ) such as TTF 1 , TTF 2 , PAX 8 play an important role in altered foetal thyroid development . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| TTF 1 , TTF 2 , Pax 8 , Na 1 symporter and thyroid peroxidase mRNA were detected . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Conversely , no relevant changes are detected in the amounts of thyroglobulin and the thyroid enriched transcription factors TTF 1 , TTF 2 , and Pax 8 . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The paired domain containing factor Pax 8 and the homeodomain containing factor TTF 1 directly interact and synergistically activate transcription . ^^^ Despite the presence of Pax 8 and TTF 1 also in a few other tissues , the simultaneous expression of the two transcription factors occurs only in the thyroid , supporting the idea that Pax 8 and TTF 1 might cooperate to influence thyroid specific gene expression . ^^^ The fusion protein GST Pax 8 is able to bind TTF 1 present in thyroid or in non thyroid cell extracts , and by using bacterial purified TTF 1 we demonstrate that the interaction is direct . ^^^ Moreover , Pax 8 and TTF 1 when co expressed in HeLa cells synergistically activate Tg gene transcription . ^^^ The synergism requires the N terminal activation domain of TTF 1 , and deletions of Pax 8 indicate that the C terminal domain of the protein is involved . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Transcription factors TTF 1 and Pax 8 control the expression of thyroid specific genes crucial for thyroid function . ^^^ The aim of this study was to investigate whether there is a correlation between TTF 1 and Pax 8 mRNA levels and type 1 or type 2 5 ' deiodinases expression in Graves ' disease . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| An expression of thyroglobulin , thyroid transcription factor 1 , and PAX 8 but not thyroid peroxidase and thyrotropin ( TSH ) receptor was detected . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Mouse knock outs have demonstrated that thyroid transcription factor 1 ( TTF 1 ) and PAX 8 are required for the survival and proliferation of thyroid follicular cell precursors , TTF 2 for their downward migration and the thyrotropin receptor ( TSHR ) for post natal thyroid growth . ^^^ However , mutations in TTF 1 , TTF 2 , PAX 8 and TSHR are found in < 10 % of patients with congenital hypothyroidism and these predominantly have orthotopic thyroid hypoplasia , often associated with other malformations . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The expression of several molecular markers essential for thyroid gland formation and function , namely Nkx2 . 1 , Pax 8 , and Titf 2 , is affected in the developing thyroid gland of Hoxa 5 ( / ) mutants . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The transcriptional control of these genes is mediated by thyroid specific transcription factors : thyroid transcription factor 1 ( TTF 1 ) and PAX 8 . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Functional analyses of the mutant protein ( PAX 8 S54G ) demonstrated that it is unable to bind a specific cis element of the thyroperoxidase gene promoter in EMSAs and that it has almost completely lost the ability to act in synergy with Titf 1 to transactivate transcription from the thyroglobulin promoter / enhancer . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The identification of transcription factors TTF 1 and Pax 8 and the demonstration of their pivotal role in thyroid development and in the control of thyroid specific gene expression , although representing remarkable openings in our understanding of cell specific transcription in the thyroid , still leave a lot of open questions . ^^^ Altogether , currently available data indicate that the regulatory machinery undergoes significant changes during thyroid organogenesis and confirm the existence of still unknown factors whose roles appear at least as critical as the ones played by TTF 1 and Pax 8 in the control of specific gene expression . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Finally , we demonstrated that only high doses of RAS oncogenes are able to inhibit the activity of Titf 1 and Pax 8 , two transcription factors essential for the maintenance of thyroid differentiation , and that the homeodomain of Titf 1 is a target of the inhibitory action of RAS . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| PAX 8 , TITF 1 , and FOXE 1 gene expression patterns during human development : new insights into human thyroid development and thyroid dysgenesis associated malformations . ^^^ Mutations in PAX 8 , TITF 1 , or FOXE 1 may account for congenital hypothyroidism in patients with either isolated TD or TD with associated malformations involving kidney , lung , forebrain , and palate . ^^^ Pax 8 , titf 1 , and foxe 1 are expressed in the mouse thyroid bud as soon as it differentiates on the pharyngeal floor . ^^^ PAX 8 and TITF 1 were first expressed in the median thyroid primordium . ^^^ They explain the malformations associated with TD in patients carrying PAX 8 , TITF 1 , and FOXE 1 gene mutations . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Ttf 1 , Ttf 2 , Pax 8 and the Tshr are expressed at early stages of thyroid development and are implicated in thyroid ontogeny . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Three of these encode transcription factors ( the thyroid transcription factors 1 and 2 ( TTF 1 or NKX2 . 1 and TTF 2 or FOXE 1 ) and PAX 8 ) while the other encodes the thyrotropin hormone receptor ( TSHR ) . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The experiments reported here analyze the expression of the transcription factors Titf 1 , Hhex , Pax 8 , and Foxe 1 in the thyroid primordium of null mutants of each of them . ^^^ |
|
| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| About 85 % of primary hypothyroidism is called thyroid digenesis and evidence suggests that mutations in transcription factors ( TTF 2 , TTF 1 , and PAX 8 ) and TSH receptor gene could be responsible for the disease . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Effects of Pax 8 and TTF 1 thyroid transcription factor gene transfer in hepatoma cells : imaging of functional protein protein interaction and iodide uptake . ^^^ The thyroid transcription factors TTF 1 and Pax 8 cooperate in the transcriptional activation of thyroid specific genes such as thyroglobulin ( Tg ) , thyroperoxidase ( TPO ) , and sodium / iodide symporter ( NIS ) . ^^^ METHODS : Dog TTF 1 ( dTTF 1 ) and the human Pax 8 ( hPax 8 ) gene were transfected in Morris hepatoma ( MH3924A ) cells to investigate ( a ) the possible visualization of functional protein protein interaction and ( b ) the induction of thyroid specific gene expression . ^^^ Imaging the transcriptional activation of the thyroid specific regulatory regions by Pax 8 and TTF 1 was possible in nude mice implanted with MHhPax8dTTF 1 cells using a cooled charge coupled device camera . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Northern blots were performed to analyze mRNA for thyroid transcription factors ( TTF 1 , TTF 2 , Pax 8 ) , and no significant changes were observed with the different treatments . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In order to determine whether TTF 1 might be involved in orbital TSHR expression , we used quantitative real time polymerase chain reaction ( PCR ) to assess relative expression of this and other thyroid associated transcription factors ( TTF 2 and Pax 8 ) in GO orbital tissue specimens ( n = 28 ) and cultures ( n = 3 ) , and in normal orbital tissues ( n = 19 ) and cultures ( n = 3 ) . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Significantly , dedifferentiated , tumoral , or Ras transformed thyrocytes fail to express DARPP 32 whereas short interfering RNA mediated silencing of DARPP 32 expression in normally differentiated thyroid cells results in loss of differentiation markers such as thyroid transcription factor 1 , Pax 8 , thyroglobulin , and the Na / I symporter . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| RESULTS : The clones overexpressing Pax 8 showed the re activation of several thyroid specific genes including NIS , Pendrin , Thyroglobulin , TPO and TTF 1 . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| PAX 8 S48F shows no defect in expression , nuclear targeting , or DNA binding and retains the ability to synergize with thyroid transcription factor 1 ( TTF 1 , NKX2 . 1 ) . ^^^ Thyroid transcription factor 1 rescues PAX8 / p300 synergism impaired by a natural PAX 8 paired domain mutation with dominant negative activity . ^^^ Reconstitution experiments in nonthyroid cells reveal that TTF 1 can partially rescue PAX 8 S48F / p300 synergism and thus reproduce the situation in thyroid cells . ^^^ Our results describe the first dominant negative missense mutation in a paired domain and provide evidence for a crucial role of the p 300 coactivator in mediating the functional synergism between PAX 8 and TTF 1 in thyroid specific gene expression . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Genes associated with thyroid gland dysgenesis include the TSH receptor in non syndromic congenital hypothyroidism , and Gsalpha and the thyroid transcription factors ( TTF 1 , TTF 2 , and Pax 8 ) , associated with different complex syndromes that include congenital hypothyroidism . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Thyroid diseases constitute a heterogeneous collection of abnormalities associated with mutations in genes responsible for the development of thyroid : thyroid transcription factor 1 ( TTF 1 ) , thyroid transcriptions factor 2 ( TTF 2 ) and PAX 8 , or in one of the genes coding for the proteins involved in thyroid hormone biosynthesis such as thyroglobulin ( TG ) , thyroperoxidase ( TPO ) , hydrogen peroxide generating system ( DUOX 2 ) , sodium / iodide symporter ( NIS ) , pendrin ( PDS ) , TSH and TSH receptor ( TSHr ) . ^^^ In a minority of these patients , the congenital hypothyroidism is associated with mutations in TTF 1 , TTF 2 , PAX 8 , TSH or TSHr genes . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In contrast , PAX 8 PPARgamma failed to stimulate transcription from the thyroglobulin promoter and blocked the synergistic stimulation of this promoter by wild type PAX 8 and thyroid transcription factor 1 . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| However , in approximately 5 % of cases , it can be a consequence of mutations in genes encoding the TSH receptor or the transcription factors TITF 1 , FOXE 1 , or PAX 8 . ^^^ We report here that in mouse models , the combination of partial deficiencies in the Titf 1 and Pax 8 genes results in an overt TD phenotype that is absent in either of the singly deficient , heterozygous mice . ^^^ The observed phenotype is strain specific , and the pattern of transmission indicates that at least two other genes , in addition to Titf 1 and Pax 8 , are necessary to generate the condition . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| The most common cause of permenant CH is thyroid dysgenesis ( 85 90 % ) in which the transcription factors TTF 1 , TTF 2 and PAX 8 would appear to be obvious candidate genes in the aetiology . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| PATIENTS AND METHODS : We examined the expression levels of transcription factors involved in thyroid development [ thyroid transcription factor 1 ( TTF 1 ) , paired box gene 8 ( PAX 8 ) and haematopoietically expressed homeobox ( HEX ) ] in 101 thyroid tissues , including 14 normal thyroid tissues , 13 hyperfunctioning tissues , 27 benign adenomas and 47 follicular or papillary carcinomas . ^^^ HEX , PAX 8 and TTF 1 gene expression in human thyroid tissues : a comparative analysis with other genes involved in iodide metabolism . ^^^ RESULTS : In benign tumours , PAX 8 and TTF 1 gene expression levels were not significantly different from the expression levels in normal tissues . ^^^ CONCLUSION : Our findings suggest that alterations in the transcription factors PAX 8 , TTF 1 and HEX gene expression , by acting individually or together , have a role in both thyroidal tumorigenesis and in the dedifferentiation process . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| We have recently demonstrated that in thyroid cells Pax 8 interacts biochemically and functionally with the transcription factor TTF 1 ( thyroid transcription factor 1 ) , and that such interaction leads to the synergistic activation of thyroglobulin ( Tg ) gene expression . ^^^ Fusion of the CC domain to Pax 8 leads to the formation of aberrant , nonfunctional high molecular mass complexes to which TTF 1 is also recruited . ^^^ The CC Pax 8 chimera inhibits the transcriptional activity of Pax 8 and of TTF 1 on both synthetic and physiological promoters and prevents the synergistic activation of the Tg promoter mediated by these two transcription factors . ^^^ Furthermore , the expression of the CC Pax 8 chimera in differentiated thyroid cells leads to the down regulation of the endogenous expression of several differentiation markers such as Tg , sodium / iodide symporter , Foxe 1 , TTF 1 , and thyroid oxidase 2 . ^^^ Moreover , by this approach , we identified Foxe 1 , TTF 1 , and thyroid oxidase 2 as new direct targets of Pax 8 or TTF 1 . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that the TG promoter mutated at the Pax 8 or TTF 1 binding element in the C site does not respond to LPS . ^^^ In band shift assays , binding of Pax 8 and TTF 1 to the C site is increased by LPS . ^^^ The Pax 8 and TTF 1 mRNA and protein levels are augmented by LPS . ^^^ The half lives of TG , Pax 8 , and TTF 1 are increased in endotoxin treated cells . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| Thyroid transcription factor 1 ( TTF 1 ) , thyroid transcription factor 2 ( TTF 2 ) and paired box gene 8 ( Pax 8 ) are demonstrated to play a crucial role for the differentiation and organogenesis of thyroid follicular cells . ^^^ Thyroid transcription factor 1 ( TTF 1 ) , thyroid transcription factor 2 ( TTF 2 ) and paired box gene 8 ( Pax 8 ) are demonstrated to play a crucial role for the differentiation and organogenesis of thyroid follicular cells . ^^^ In conclusion , abnormal expression of TTF 1 , TTF 2 and Pax 8 was closely related to thyroid tumorigenesis . . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| In mammals , expression of NIS is stimulated by TSH and transcription of the NIS gene involves regulation by the thyroid specific transcription factors Pax 8 and Nkx2 . 1 . ^^^ In this study , we examined the mRNA expression of NIS , Pax 8 and Nkx2 . 1 in the thyroid gland of Xenopus laevis tadpoles by semi quantitative reverse transcriptase ( RT ) PCR . ^^^ In addition , it could be shown that thyroid glands of 10 . laevis tadpoles express Pax 8 and Nkx2 . 1 mRNA in a developmentally regulated manner and that ex vivo treatment of thyroid glands with bTSH , forskolin , and cAMP analogs increased the expression of Pax 8 and Nkx2 . 1 mRNA . ^^^ |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q06710 and P43699 |
Pubmed |
SVM Score :0.0 |
| NA |
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