| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.55836274 |
| The transcriptional repressor PLZF was identified by its translocation with retinoic acid receptor alpha in t ( 11 ; 17 ) acute promyelocytic leukemia ( APL ) . 0.55836274^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.54314651 |
| We demonstrate that RARalpha PLZF can interfere with PLZF transcriptional repression and that this is critical for APL pathogenesis , since leukemias in PLZF ( / ) / PLZF RARalpha mutants and in PLZF RARalpha / RARalpha PLZF TM are indistinguishable . 0.54314651^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Promyelocyte Leukemia Zinc Finger ( PLZF ) is a Kruppel like zinc finger gene previously identified in a unique case of acute promyelocytic leukemia ( APL ) as the counterpart of a reciprocal chromosomal translocation involving the retinoic acid receptor alpha gene ( RAR alpha ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| A variant translocation t ( 11 ; 17 ) has also been discovered in a subset of APL which fuses RAR alpha to a new gene , PLZF on chromosome 11q23 . ^^^ Both PML / RAR alpha and PLZF / RAR alpha display the `` dominant negative ' ' effect on the wild type RAR / RXR . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| This time RAR alpha is fused to a new gene , PLZF , on chromosome 11q23 . ^^^ It has been shown that the PLZF RAR alpha , like PML RAR alpha , has a `` dominant negative ' ' effect on the wild type RAR RXR . ^^^ The comparison of the biological activities mediated by PML RAR alpha and PLZF RAR alpha may give new insights into the pathogenesis as well as the mechanisms of ATRA induced differentiation in APL . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Analysis of a variant translocation t ( 11 ; 17 ) in a case of acute promyelocytic leukemia ( APL ) led to discovery of a novel zinc finger gene , PLZF , fused to the retinoic acid receptor alpha ( RAR alpha ) gene . ^^^ All six patients had PLZF RAR alpha gene fusion as detected by reverse transcription / polymerase chain reaction assay , Southern blotting , or pulsed field gel electrophoresis . ^^^ APL associated with t ( 11 ; 17 ) and fusion of the PLZF and RAR alpha genes is a discrete clinico pathologic syndrome with a distinctly worse prognosis than t ( 15 ; 17 ) APL . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| To investigate the potential biological role ( s ) of the PLZF gene , discovered as a fusion with the RARA locus in a patient with acute promyelocytic leukemia harboring a t ( 11 ; 17 ) chromosomal translocation , we have isolated its murine homologue ( mPLZF ) and studied its patterns of developmental expression . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Translocation of the RAR alpha locus to the PML or PLZF gene in acute promyelocytic leukaemia . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Several cases of APML with t ( 11 ; 17 ) have recently been described , involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| It is also important to determine the function ( s ) of PLZF and PLZF / RAR alpha , and determine whether other APL patients with mutations involving PML or RAR alpha ( but not both ) respond to therapy with all trans RA . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| PLZF RAR alpha fusion proteins generated from the variant t ( 11 ; 17 ) ( q 23 ; q 21 ) translocation in acute promyelocytic leukemia inhibit ligand dependent transactivation of wild type retinoic acid receptors . ^^^ Recently , we described a recurrent variant translocation , t ( 11 ; 17 ) ( q 23 ; q 21 ) , in acute promyelocytic leukemia ( APL ) which juxtaposes PLZF , a gene encoding a zinc finger protein , to RARA , encoding retinoic acid receptor alpha ( RAR alpha ) . ^^^ We have now cloned cDNAs encoding PLZF RAR alpha chimeric proteins and studied their transactivating activities . ^^^ In transient expression assays , both the PLZF ( A ) RAR alpha and PLZF ( B ) RAR alpha fusion proteins like the PML RAR alpha protein resulting from the well known t ( 15 ; 17 ) translocation in APL , antagonized endogenous and transfected wild type RAR alpha in the presence of retinoic acid . ^^^ Cotransfection assays showed that a significant repression of RAR alpha transactivation activity was obtained even with a very low PLZF RAR alpha expressing plasmid concentration . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Poor response to all trans retinoic acid therapy in a t ( 11 ; 17 ) PLZF / RAR alpha patient . ^^^ Recently the RAR alpha gene has been demonstrated to be involved in a novel fusion transcript ( PLZF / RAR alpha ) through a t ( 11 ; 17 ) translocation . ^^^ We describe here the second case of such a patient with a t ( 11 ; 17 ) PLZF / RAR alpha leukemic clone . ^^^ Southern analysis revealed that the breakpoint in the RAR alpha gene was within the second intron ( as for PML / RAR alpha ) and the intron separating the second and third zinc finger of the PLZF gene . ^^^ These results suggest that the t ( 11 ; 17 ) ( PLZF / RAR alpha ) case of this study was less responsive to ATRA therapy than t ( 15 ; 17 ) ( PML / RAR alpha ) cases and raises the question of the definition of this novel AML subtype . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL , further implicating the RAR alpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Further molecular analysis of this patient showed a rearrangement between the RAR alpha gene and a newly discovered zinc finger gene named PLZF ( promyelocytic leukemia zinc finger ) . ^^^ The fusion PLZF RAR alpha gene found in this case , was not found in DNA obtained from the bone marrow of normals , APL with t ( 15 ; 17 ) and in one patient with AML M 2 with a t ( 11 ; 17 ) . ^^^ Partial exon / intron structure of the PLZF gene flanking the break point on chromosome 11 was also established and the breakpoint within the RAR alpha gene was mapped approximately 2 kb downstream of the exon encoding the 5 ' untranslated region and the unique A 2 domain of the RAR alpha 2 isoform . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The PLZF gene was discovered by studying a rearrangement of the RAR alpha locus in a patient with acute promyelocytic leukemia and a t ( 11 ; 17 ) chromosomal translocation . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In a few cases RAR alpha variably translocates to chromosome 11 , where it fuses to the PLZF gene or to a gene , also on 11 , which has not yet been characterized . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The RAR alpha PLZF chimera associated with Acute Promyelocytic Leukemia has retained a sequence specific DNA binding domain . ^^^ In a rare APL syndrome associated with t ( 11 ; 17 ) , fusion of the RAR alpha gene with the PLZF gene , encoding a Zinc finger protein produces two reciprocal RAR alpha chimeras . ^^^ Although PLZF RAR alpha and PML RAR alpha are similar in their apparent dominant negative effects , t ( 11 ; 17 ) associated APL is refractory to ATRA therapy . ^^^ Using these autonomously transactivating hybrids , similar in structure to the RAR alpha PLZF fusion , we mapped the DNA binding domain of PLZF to the last five Zinc fingers , a region retained in RAR alpha PLZF chimera and characterized a specific PLZF target sequence . ^^^ Our data support the hypothesis that RAR alpha PLZF chimera is not an inert product of reciprocal translocation and may thus contribute to ATRA unresponsiveness of t ( 11 ; 17 ) associated APL . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In t ( 11 ; 17 ) the PLZF gene , encoding a Krppel like zinc finger protein , is fused to the retinoic acid receptor alpha ( RAR alpha ) gene , yielding two classes of chimeric proteins . ^^^ The reciprocal PLZF RAR alpha and RAR alpha PLZF fusion proteins were localized to the nucleus both in the presence and absence of ATRA . ^^^ PLZF RAR alpha , in combination with the retinoid 10 receptor ( RXR ) bound to a retinoic acid responsive element ( RARE ) less efficiently than RAR alpha and formed multimeric DNA protein complexes . ^^^ PLZF RAR alpha stimulated ATRA dependent transcription of RARE containing reporter genes with diminished activity compared to wild type RAR alpha . ^^^ In addition , PLZF RAR alpha antagonized the function of coexpressed wild type RAR alpha , an effect relieved by over expression of RXR . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukaemia ( APL ) , associated with chromosomal translocations involving the retinoic acid receptor alpha gene ( RARA ) and the PML gene , is sensitive to retinoic acid ( RA ) treatment , while APL patients harbouring translocations between RARA and the PLZF gene do not respond to RA . ^^^ We have generated PML RARA and PLZF RARA transgenic mice and show here that these fusion proteins play a critical role in leukaemogenesis and in determining responses to RA in APL , because PLZF RARA transgenic mice develop RA resistant leukaemia , while PML RARA mice are responsive to RA treatment . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| However , treatment with RA induces differentiation of leukaemic blast cells and disease remission in PML RARalpha APLs , whereas PLZF RARa APLs are resistant to RA . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Opposite effects of the acute promyelocytic leukemia PML retinoic acid receptor alpha ( RAR alpha ) and PLZF RAR alpha fusion proteins on retinoic acid signalling . ^^^ Fusion proteins involving the retinoic acid receptor alpha ( RAR alpha ) and the PML or PLZF nuclear protein are the genetic markers of acute promyelocytic leukemias ( APLs ) . ^^^ APLs with the PML RAR alpha or the PLZF RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid ( RA ) induced differentiation : PML RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment , while patients with PLZF RAR alpha do not . ^^^ These data demonstrate that PML RAR alpha and PLZF RAR alpha have similar ( inhibitory ) effects on RA independent differentiation and opposite ( stimulatory or inhibitory ) effects on RA dependent differentiation and that they behave in vivo as RA dependent enhancers or inhibitors of RA responsive genes , respectively . ^^^ Their different activities on the RA signalling pathway might underlie the different responses of PML RAR alpha and PLZF RAR alpha APLs to RA treatment . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Two rare variants of APL have been described , in which RARA is fused to one of two other genes , PLZF and NPM . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In a few cases , RAR alpha variably translocates to chromosome 11 where it fuses to the PLZF gene or to a newly described partner , NuMA . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Cases with t ( 11 ; 17 ) ( q 23 ; q 21 ) which fuses the PLZF and RARA genes do not respond to ATRA . ^^^ We described previously an APL case with an unbalanced t ( 5 ; 17 ) implicating RARA but neither PML nor PLZF . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In a small subset of acute promyelocytic like leukaemias ( APL L ) , RARA is fused to a different partner : the pro myelocytic leukaemia zinc finger ( PLZF ) gene on 11q23 , the nucleophosmin ( NPM ) gene on 5q35 or the nuclear mitotic apparatus ( NuMA ) gene on 11q13 . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukaemia is characterized by translocations that involve the retinoic acid receptor alpha ( RAR alpha ) locus on chromosome 17 and the PML locus on 15 or the PLZF locus on 11 . ^^^ The resulting abnormal translocation products encode for PML / RAR alpha or PLZF / RAR alpha fusion proteins . ^^^ There is increasing experimental evidence that the APL specific fusion proteins have similar biologic activities on differentiation and survival and that both components of the fusion proteins ( PML or PLZF and RAR alpha ) are indispensable for these biological activities . ^^^ We report here immunofluorescence studies on the cellular localization of PLZF and PLZF / RAR alpha and compare it with the localization of PML and PML / RAR alpha . ^^^ The localization of PLZF / RAR alpha is different to that of PLZF and RAR alpha . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukemia ( APL ) originate from chromosomal translocations generating two types of fusion proteins both involving the retinoic acid receptor alpha ( RAR alpha ) and either the gene PML ( t ( 15 ; 17 ) ) or PLZF ( t ( 11 ; 17 ) ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The demonstration , in transgenic mice , that PML RAR alpha ( and PLZF RAR alpha ) can disrupt normal hematopoiesis and , given sufficient time , cause an APL like syndrome . the variation in phenotype of the mice , which appears to be a consequence of the specific expression vector used , emphasizes the cell type specific nature of PML RAR alpha function . ^^^ Continuing functional analysis of PML , PLZF , and RAR alpha . ^^^ In particular , the demonstration that PML and PLZF can form heterodimers provides a critical functional link between these proteins and offers a tantalizing glimpse at how both , when linked with RAR alpha , can cause APL . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Finally , ETO interacted with PLZF / RAR alpha and enhanced its ability to repress through the RARE . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In contrast , PML RARalpha and PLZF RARa display an enhanced ability to form homodimers , and this enhanced homodimer formation is believed to contribute to the neoplastic properties of these chimeric oncoproteins . ^^^ We report here that the DNA recognition specificity of the RXRalpha / RARa heterodimer , which is presumed to be the dominant receptor species in normal cells , differs from that of the PML RARalpha and PLZF RARalpha homodimers , which are thought to prevail in the oncogenic cell . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukemia ( APL ) is associated with chromosomal translocations , invariably involving the retinoic acid receptor alpha ( RAR alpha ) gene fused to one of several distinct loci , including the PML or PLZF genes , involved in t ( 15 ; 17 ) or t ( 11 ; 17 ) , respectively . ^^^ The PML RAR alpha and PLZF RAR alpha fusion oncoproteins function as aberrant transcriptional repressors , in part by recruiting nuclear receptor transcriptional corepressors and histone deacetylases ( HDACs ) . ^^^ In cells from PLZF RAR alpha / RAR alpha PLZF transgenic mice and cells harboring t ( 15 ; 17 ) , HDACIs induced apoptosis and dramatic growth inhibition , effects that could be potentiated by RA . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Comparative analysis of genes regulated by PML / RAR alpha and PLZF / RAR alpha in response to retinoic acid using oligonucleotide arrays . ^^^ Acute promyelocytic leukemia ( APL ) is associated with chromosomal translocations involving retinoic acid receptor alpha ( RAR alpha ) and its fusion partners including promyelocytic leukemia ( PML ) and promyelocytic leukemia zinc finger ( PLZF ) . ^^^ Using oligonucleotide arrays , we examined changes in global gene expression mediated by the ectopic expression of either PML / RAR alpha ( retinoid sensitive ) or PLZF / RAR alpha ( retinoid resistant ) in U 937 cells . ^^^ RA strongly up regulated these genes in PML / RAR alpha , but not in PLZF / RAR alpha expressing U 937 cells . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Leukemia with distinct phenotypes in transgenic mice expressing PML / RAR alpha , PLZF / RAR alpha or NPM / RAR alpha . ^^^ The RAR alpha gene fuses to variable partners ( PML , PLZF , NPM , NuMA and STAT5B : 10 genes ) leading to the expression of APL specific fusion proteins with identical RAR alpha moieties . ^^^ We compared the features of the leukemia observed in these TM with those in hCG PML / RAR alpha and hCG PLZF / RAR alpha TM . ^^^ Similarly , hCG PLZF / RAR alpha TM displayed a different phenotype where terminally differentiated myeloid cells predominated . ^^^ Importantly , the NPM / RAR alpha oncoprotein was found to localize in the nucleolus , unlike PML / RAR alpha and PLZF / RAR alpha , thus possibly interfering with the normal function of NPM . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Leukemia associated retinoic acid receptor alpha fusion partners , PML and PLZF , heterodimerize and colocalize to nuclear bodies . ^^^ In acute promyelocytic leukemia ( APL ) , the typical t ( 15 ; 17 ) and the rare t ( 11 ; 17 ) translocations express , respectively , the PML / RARalpha and PLZF / RARalpha fusion proteins ( where RARalpha is retinoic acid receptor alpha ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| A prototypic human BTB / POZ protein , PLZF ( promyelocytic leukemia zinc finger ) is fused to RARalpha ( retinoic acid receptor alpha ) in a subset of acute promyelocytic leukemias ( APLs ) , where it acts as a potent oncogene . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The human PLZF ( promyelocytic leukaemia zinc finger ) gene encodes a Krppel like zinc finger protein , which was identified via the reciprocal translocation t ( 11 ; 17 ) ( q 23 ; q 21 ) fusing it to the retinoic acid receptor alpha ( RARalpha ) gene in promyelocytic leukaemia . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The promyelocytic leukemia zinc finger ( PLZF ) protein is a sequence specific DNA binding transcriptional factor fused to retinoic acid receptor alpha in acute promyelocytic leukemia associated with the ( 11 ; 17 ) ( q 23 ; q 21 ) translocation . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| One form of APL is associated with the translocation t ( 11 ; 17 ) , which joins the promyelocytic leukemia zinc finger ( PLZF ) and retinoic acid receptor alpha ( RARalpha ) genes . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The PLZF ( promyelocytic leukemia zinc finger ) transcriptional repressor , when fused to retinoic acid receptor alpha ( RARalpha ) , causes a refractory form of acute promyelocytic leukemia . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The Retinoic acid receptor alpha ( RARalpha ) chimeric proteins PML , PLZF , NPM , and NuMA RARalpha have distinct intracellular localization patterns . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t ( 11 ; 17 ) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia ( APL ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Fusion proteins involving the retinoic acid receptor alpha ( RARalpha ) and PML or PLZF nuclear protein are the genetic markers of acute promyelocytic leukemia ( APL ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| For example , in acute promyelocytic leukaemia ( APL ) , reciprocal chromosomal translocations involving the retinoic acid receptor alpha ( RARalpha ) gene lead to the formation of two fusion genes : 10 RARalpha and RARalpha 10 ( where 10 is the alternative RARalpha fusion partner : PML , PLZF , NPM , NuMA and STAT 5b ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukaemia ( APL ) is characterised by chromosomal rearrangements of 17q21 , leading to fusion of the gene encoding retinoic acid receptor alpha ( RARalpha ) to a number of alternative partner genes ( 10 ) , the most frequent of which are PML ( > 95 % ) , PLZF ( 0 . 8 % ) and NPM ( 0 . 5 % ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N CoR TBLR 1 corepressor complex to repress transcription in vivo . ^^^ Fusion proteins of retinoic acid receptor alpha ( RARalpha ) with promyelocytic leukemia protein ( PML RARalpha ) or with promyelocytic leukemia zinc finger protein ( PLZF RARalpha ) are associated with and likely responsible for the development of acute promyelocytic leukemia . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Promyelocytic leukemia zinc finger ( PLZF ) protein is a sequence specific DNA binding protein that represses the transcriptional activity of target genes such as those for cyclin A and the interleukin 3 receptor alpha chain . ^^^ The PLZF gene becomes fused to the retinoic acid receptor alpha gene as a result of the t ( 11 , 17 ) ( q 23 ; q 21 ) chromosomal translocation that is associated with acute promyelocytic leukemia . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Promyelocytic leukemia zinc finger ( PLZF ) , originally identified as a fusion with retinoic acid receptor alpha in rare cases of all trans retinoic acid resistant acute promyelocytic leukemia , is a transcriptional repressor that recruits histone deacetylase containing corepressor complexes to specific DNA binding sites . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| This phenotype is induced by specific acute myeloid leukemia associated translocations , such as t ( 15 ; 17 ) and t ( 11 ; 17 ) , which involve an identical portion of the retinoic acid receptor alpha ( RARalpha ) and either the promyelocytic leukemia ( PML ) or promyelocytic zinc finger ( PLZF ) genes , respectively . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Both PML and PLZF RARalpha possess identical RAR sequences and inhibit ATRA induced gene transcription as well as cell differentiation . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Promyelocytic leukemia zinc finger retinoic acid receptor a ( PLZF RARalpha ) , a fusion receptor generated as a result of a variant t ( 11 ; 17 ) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia ( APL ) patients , has been shown to display a dominant negative effect against the wild type RARalpha / retinoid 10 receptor alpha ( RXRalpha ) . ^^^ We now show that its N terminal region ( called the POZ domain ) , which mediates protein protein interaction as well as specific nuclear localization of the wild type PLZF and chimeric PLZF RARalpha proteins , is primarily responsible for this activity . ^^^ To further investigate the mechanisms of PLZF RARalpha action , we have also studied its ligand receptor , protein protein , and protein DNA interaction properties and compared them with those of the promyelocytic leukemia gene ( PML ) RARalpha , which is expressed in the majority of APLs as a result of t ( 15 ; 17 ) translocation . ^^^ PLZF RARalpha and PML RARalpha have essentially the same ligand binding affinities and can bind in vitro to retinoic acid response elements ( RAREs ) as homodimers or heterodimers with RXRalpha . ^^^ PLZF RARalpha homodimerization and heterodimerization with RXRalpha were primarily mediated by the POZ domain and RARalpha sequence , respectively . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| A small number of variant APL translocations have also been shown to involve rearrangements that fuse RARalpha to partner genes other than PML , namely PLZF , NPM , and NuMA . ^^^ We further explored the effects of the NPM RARalpha chimeric protein on the subcellular localization of PML , RXRalpha , NPM , and PLZF using immunofluorescent confocal microscopy . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| SMRT corepressor interacts with PLZF and with the PML retinoic acid receptor alpha ( RARalpha ) and PLZF RARalpha oncoproteins associated with acute promyelocytic leukemia . ^^^ Human acute promyelocytic leukemia , for example , is tightly linked to chromosomal translocations that fuse novel amino acid sequences ( denoted PML , PLZF , and NPM ) to the DNA binding and hormone binding domains of RARalpha . ^^^ We report here that the PML RARalpha and PLZF RARalpha oncoproteins retain the ability of RARalpha to associate with corepressors , and that this corepressor association correlates with certain aspects of the leukemic phenotype . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The translocation fuses the RARalpha gene to the PLZF gene , resulting in the formation of reciprocal fusion proteins , hypothesized to play prominent roles in leukemogenesis . ^^^ Promyelocytic leukemia zinc finger ( PLZF ) encodes a transcription factor with nine Krppel like zinc fingers , seven of which are retained in the t ( 11 ; 17 ) fusion protein RARalpha PLZF . ^^^ In contrast , the RARalpha PLZF protein activated transcription of a promoter containing a PLZF response element . ^^^ These results suggest that RARalpha PLZF , generated in acute promyelocytic leukemia , is an aberrant transcription factor that can deregulate the expression of PLZF target genes and contribute to leukemogenesis . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Mutant forms of RARalpha , created by chromosomal translocations with either the PML ( for promyelocytic leukaemia ) or the PLZF ( for promyelocytic leukaemia zinc finger ) locus , are oncogenic and result in human acute promyelocytic leukaemia ( APL ) . ^^^ PML RARalpha APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids ( RA ) ; in contrast , PLZF RARalpha patients respond very poorly , if at all . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF , PLZF RARalpha , and BCL 6 . ^^^ We and others have previously implicated the SMRT corepressor in the actions of the PLZF transcription factor and in the function of its oncogenic derivative , PLZF retinoic acid receptor ( RARalpha ) , in promyelocytic leukemia . ^^^ Furthermore , we demonstrate that the oncogenic PLZF RARalpha chimera lacks several important corepressor interaction sites that are present in the native PLZF protein . ^^^ Thus the t ( 11 ; 17 ) translocation that creates the PLZF RARalpha chimera generates an oncoprotein with potentially novel regulatory properties distinct from those of either parental protein . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The PLZF gene was identified by its fusion with the RARalpha locus in a therapy resistant form of acute promyelocytic leukemia ( APL ) associated with the t ( 11 ; 17 ) ( q 23 ; q 21 ) translocation . ^^^ In contrast RARalpha PLZF , a fusion protein generated in t ( 11 ; 17 ) ( q 23 ; q 21 ) APL activates cyclin A 2 transcription and allows expression of cyclin A in anchorage deprived NIH3T3 cells . ^^^ Deregulation of cyclin A 2 by RARalpha PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t ( 11 ; 17 ) ( q 23 ; q 21 ) associated APL . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF RARalpha and NPM RARalpha . ^^^ Acute promyelocytic leukemia ( APL ) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners : PML , PLZF , NPM , and NuMA genes . ^^^ To study the leukemogenic potential of the fusion genes in vivo , we generated transgenic mice with PLZF RARalpha and NPM RARalpha . ^^^ PLZF RARalpha transgenic animals developed chronic myeloid leukemia like phenotypes at an early stage of life ( within 3 months in five of six mice ) , whereas three NPM RARalpha transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life ( from 12 to 15 months ) . ^^^ In contrast to bone marrow cells from PLZF RARalpha transgenic mice , those from NPM RARalpha transgenic mice could be induced to differentiate by all trans retinoic acid ( ATRA ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| As a consequence of the translocation RARalpha variably fuses to the PML , PLZF , NPM and NUMA genes ( 10 genes ) , leading to the generation of RARalpha 10 and 10 RARalpha fusion genes . ^^^ Furthermore , APL associated with translocation between the RARalpha and the PLZF genes ( PLZF RARalpha ) shows a distinctly worse prognosis with poor response to chemotherapy and little or no response to treatment with RA , thus defining a new APL syndrome . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The impact of differential binding of wild type RARalpha , PML , PLZF and NPM RARalpha fusion proteins towards transcriptional co activator , RIP 140 , on retinoic acid responses in acute promyelocytic leukemia . ^^^ The difference in response to ATRA therapy between acute promyelocytic leukemia ( APL ) patients with PML RARalpha fusion and PLZF RARalpha fusion has recently been found to be partially due to the strong association of the transcriptional co repressor , SMRT / N CoR , with PLZF domain . ^^^ Moreover , we show for the first time that the interaction between the transcriptional co activator , RIP 140 , and PML , PLZF or NPM RARalpha fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild type RARalpha . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| RARalpha fuses to the PML gene in the vast majority of APL cases , and in a few cases to the PLZF , NPM , NuMA and Stat5b genes , respectively , leading to the generation of RARalpha 10 : and 10 : RARalpha fusion genes . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| As a consequence of the translocation , RARalpha variably fuses to the PML , PLZF , NPM , NuMA , and Stat5b genes ( 10 genes ) , respectively , leading to the generation of RARalpha 10 and 10 RARalpha fusion genes . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Here we review how a detailed analysis of the functions of two of these RARalpha partners , the promyelocytic leukemia ( PML ) and promyelocytic leukemia zinc finger ( PLZF ) proteins , has allowed a greater understanding of the molecular mechanisms implicated in APL pathogenesis . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| RARalpha variably fuses to PML , PLZF , NPM , NuMA , and Stat5B genes ( 10 genes / proteins ) . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Retinoic acid ( RA ) and As2O3 treatment in transgenic models of acute promyelocytic leukemia ( APL ) unravel the distinct nature of the leukemogenic process induced by the PML RARalpha and PLZF RARalpha oncoproteins . ^^^ Acute promyelocytic leukemia ( APL ) is associated with chromosomal translocations always involving the RARalpha gene , which variably fuses to one of several distinct loci , including PML or PLZF ( 10 genes ) in t ( 15 ; 17 ) or t ( 11 ; 17 ) , respectively . ^^^ In contrast , neither in PLZF RARalpha transgenic mice nor in nude mice transplanted with PLZF RARalpha cells did any of the three regimens induce complete disease remission . ^^^ Unexpectedly , therapeutic doses of RA and RA + As ( 2 ) O ( 3 ) can induce , both in vivo and in vitro , the degradation of either PML RARalpha or PLZF RARalpha proteins , suggesting that the maintenance of the leukemic phenotype depends on the continuous presence of the former , but not the latter . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Acute promyelocytic leukemia with a PLZF RARalpha fusion protein . ^^^ Four variant mutations have been described , and the t ( 11 ; 17 ) ( q 21 ; q 23 ) translocation generating a promyelocyte leukemia zinc finger ( PLZF ) RARalpha fusion gene is the most common . ^^^ PLZF RARalpha positive APL forms a clinically distinct group because unlike PML RARalpha positive leukemia , it does not respond to retinoic acid with terminal granulocytic differentiation of the cells , and remissions can not be achieved with retinoids alone . ^^^ Targeting of the PLZF RARalpha bound corepressor complexes using a combination of all trans retinoic acid ( ATRA ) and deacetylase inhibitors has shown that the repression of target genes can be relieved , allowing differentiation of the cells . ^^^ Together , these findings indicate that PLZF RARalpha positive leukemia is not completely resistant to differentiation induction if the proper costimuli are given . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| RARalpha variably fuses to the PML , PLZF , NPM , NuMA , and STAT 5b genes ( 10 genes ) , leading to the generation of 10 RARalpha and RARalpha 10 fusion genes . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| The translocation of RARalpha with PML or PLZF genes in acute promyelocytic leukemia is a paradigm of the role of RARs in cancer biology . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In other cases of t ( 15 ; 17 ) negative APL , various chromosomal rearrangements involving 17q21 have been documented leading to fusion of RARalpha to alternative partners , namely PLZF , NPM , NuMA and STAT5b . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| RARalpha fuses to the PML gene in the vast majority of APL cases , and in a few cases to the PLZF , NPM , NuMA and STAT5b genes respectively . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| RARalpha fuses to the PML gene in the vast majority of APL cases , and in a few cases to the PLZF , NPM , NuMA and STAT5b genes . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Down stream regions of the POZ domain influence the interaction of the t ( 11 ; 17 ) associated PLZF / RARalpha fusion protein with the histone deacetylase recruiting co repressor complex . ^^^ INTRODUCTION : Acute promyelocytic leukemia ( APL ) patients with t ( 15 ; 17 ) ( PML / RARalpha positive ) achieve remission upon t RA treatment , whereas patients with t ( 11 ; 17 ) ( PLZF / RARalpha positive ) do not . ^^^ Differently to PML / RARalpha , PLZF / RARalpha also binds the HD NCR in a ligand independent manner through the PLZF portion of the fusion protein ( PLZF # ) , which seems to be crucial for the t RA resistance of t ( 11 ; 17 ) APL patients . ^^^ The interaction between HD NCR and PLZF / RARalpha was investigated by in vitro binding assays . ^^^ RESULTS : ( 1 ) Deletions in PLZF # convert PLZF / RARalpha from a repressor to an activator of t RA response in U 937 cells ; ( 2 ) the effect of PLZF / RARalpha on t RA signaling is regulated by the POZ domain and its down stream regions of PLZF # ; ( 3 ) there are additional binding sites for HD NCR in PLZF # and ( 4 ) PLZF # not only directly binds but also regulates the binding of PLZF / RARalpha to the HD NCR . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Although STAT5b RARalpha had no effect on ligand induced STAT5b activation , it enhanced interleukin 6 induced STAT 3 dependent reporter activity , an effect shared by other APL fusion proteins including promyelocytic leukemia RARalpha and promyelocytic leukemia zinc finger ( PLZF ) RARalpha . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the eor 1 and eor 2 mutant backgrounds reveal an essential role for the Elk 1 related gene lin 1 . eor 1 and eor 2 also act downstream or in parallel to pry 1 Axin and therefore act at the convergence of the Ras and Wnt pathways . eor 1 encodes the ortholog of human PLZF , a BTB / zinc finger transcription factor that is fused to RARalpha in acute promyelocytic leukemia . eor 2 encodes a novel protein . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| Like gag RXRbeta , the oncogenic PLZF RARalpha fusion protein also antagonizes TGF beta induced growth inhibition , and the fusion between PLZF and RARalpha is essential for resistance to TGF beta . ^^^ Moreover , TGF beta and retinoic acid ( RA ) cooperatively induce growth inhibition as well as transcription of the p 15 ( ink4b ) gene , while PLZF RARalpha represses TGF beta induced expression of the p 15 ( ink4b ) gene . ^^^ Together , these results suggest that the TGF beta and RA pathways cooperate to inhibit cell growth and that PLZF RARalpha mediated resistance to TGF beta may facilitate the development of the PLZF RARalpha induced leukemia . . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Promyelocytic leukemia zinc finger protein ( PLZF ) was initially identified by virtue of its fusion with RARalpha as a result of a variant t ( 11 ; 17 ) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia ( APL ) patients . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| In some acute leukaemias , a chromosomal translocation fusing the PLZF gene to that encoding the retinoic acid receptor RARalpha gives rise to a fusion protein , PLZF RARalpha , thought to be responsible for constitutive repression of differentiation associated genes in these cells . ^^^ Repression by both PLZF and PLZF RARalpha is sensitive to the histone deacetylase inhibitor TSA , and PLZF was previously shown to interact physically with HDAC 1 , a class 1 histone deacetylase . ^^^ We here asked whether class 2 histone deacetylases , known to be generally involved in differentiation processes , participate in the repression mediated by PLZF and PLZF RARalpha , and found that PLZF interacts with HDAC 4 in both GST pull down and co immunoprecipitation assays . ^^^ Furthermore , HDAC 4 is indeed involved in PLZF and PLZF RARalpha mediated repression , since an enzymatically dead mutant of HDAC 4 released the repression , as did an siRNA that blocks HDAC 4 expression . ^^^ |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10276 and Q05516 |
Pubmed |
SVM Score :0.0 |
| NA |
|