Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.56621699 |
Both AG 1478 and U 0126 also restored the tamoxifen mediated association of ER with nuclear receptor corepressor ( N CoR ) in the antiestrogen resistant MCF 7 cells . 0.56621699^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.77421 |
Tamoxifen bound ERalpha associates with nuclear receptor corepressor ( N CoR ) and silencing mediator for retinoid and thyroid hormone receptors ( SMRT ) at certain target genes . 0.77421^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Several lines of evidence indicate that the nuclear receptor corepressor ( N CoR ) complex imposes ligand dependence on transcriptional activation by the retinoic acid receptor and mediates the inhibitory effects of estrogen receptor antagonists , such as tamoxifen , suppressing a constitutive N terminal , Creb binding protein / coactivator complex dependent activation domain . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
SAP 30 also binds the N CoR corepressor and is required for N CoR mediated repression by antagonist bound estrogen receptor and the homeodomain protein Rpx , as well as N CoR suppression of transactivation by the POU domain protein Pit 1 . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
To obtain some clue to these roles , we screened the expression levels of ER alpha , ER beta , coactivators ( SRC 1 , TIF 2 , AIB 1 , CBP , and P / CAF ) and corepressors ( N CoR and SMRT ) in 6 normal mammary glands , 6 intraductal carcinomas , 22 invasive ductal carcinomas , and 7 breast cancer cell lines using a multiplex reverse transcription PCR . ^^^ A significant correlation of expression levels was observed between ER alpha and TIF 2 , AIB 1 , P / CAF , and N CoR , and between ER beta and AIB 1 and CBP in the tissue samples . ^^^ In addition , the expression levels of ER alpha and N CoR were significantly higher in the intraductal carcinomas than those in the invasive ductal carcinomas . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
These results suggest that ER alpha Delta AF 2 and similar mutant receptors recently found associated with certain tumors may actively perturb the normal E ( 2 ) signaling via SWI / SNF , N CoR / SMRT , and HDAC . . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Several lines of evidence have indicated that tamoxifen promotes association between ERalpha and corepressors N CoR or silencing mediator for retinoid and thyroid hormone receptor ( SMRT ) . ^^^ Our results indicate that N CoR / SMRT recognize and interact with helices H 3 and H 5 of the ERalpha ligand binding domain in a 4 hydroxy tamoxifen dependent manner . ^^^ The mutant ERalpha ( D351Y ) , derived from a tamoxifen stimulated tumor and containing an amino acid substitution at position 351 within H 3 , showed reduced interaction with N CoR / SMRT and high tamoxifen induced activation function 1 ( AF 1 ) activity . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Deletion of helix 12 increased N CoR binding by the TR modestly , and by the RXR and ER to a much greater extent , indicating a competition between this helix and the corepressor that regulates the extent of corepressor binding by nuclear receptors . ^^^ When helix 12 was deleted , N CoR binding by the ER was stimulated by tamoxifen , and binding by the TR was stimulated by Triac , indicating that helix 12 is not the only feature that regulates corepressor binding . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Notably , tamoxifen induced association of ER with the transcriptional corepressors N CoR or SMRT was reduced in HER 2 overexpressing breast tumor cells but not in cells with low HER 2 levels . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Moreover , ICI and raloxifene are more efficient than tamoxifen in promoting ERalpha binding to the corepressor N CoR in vivo and in vitro . ^^^ An ERalpha mutation ( 537X ) that increases N CoR binding in the presence of all SERMs blocks AF 1 activity . ^^^ An ERalpha mutation ( L379R ) that decreases N CoR binding increases AF 1 activity in the presence of ICI and raloxifene and reverses the effect of the 537X mutation . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Previous studies have implicated a complex containing the nuclear receptor corepressor ( N CoR ) in the mechanism by which tamoxifen represses ER mediated transcriptional activity . ^^^ In the present study a truncated N CoR construct was used to inhibit endogenous N CoR activity in an ER positive breast cancer cell line . ^^^ This dominant negative N CoR was successful in relieving repression conferred by the unliganded retinoic acid receptor , but it failed to affect the transcriptional activity of the ER in the presence of tamoxifen . ^^^ In conclusion , these results may reveal that N CoR affects tamoxifen liganded ER in a manner distinct from its influence on retinoic acid receptor mediated transcriptional activity or that corepressors other than N CoR may be involved in the ability of tamoxifen to repress estrogen responsive transcription and tumor growth . . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
In vivo and in vitro binding assays revealed that whereas 4 hydroxytamoxifen ( OHT ) induced binding of ERalpha to both an AF 1 coactivator complex ( p68 / p72 and p 300 ) and corepressor complexes ( N CoR / SMRT ) , BBP selectively enhanced the binding to the AF 1 coactivators . ^^^ Expression of a dominant negative type of N CoR inhibited the interaction between OHT bound ERalpha and N CoR / SMRT and enhanced the transcriptional activity of OHT bound ERalpha . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Furthermore , reinitiation of cell cycle progression by insulin / insulin like growth factor 1 in hydroxytamoxifen arrested cells involves dissociation of the corepressors nuclear receptor corepressor ( N CoR ) and silencing mediator for retinoid and thyroid hormone receptor ( SMRT ) from nuclear estrogen receptor alpha and redistribution to the cytoplasm , a process that is inhibited by mitogen activated protein / extracellular signal regulated kinase , but not phosphatidylinositol 3 ' kinase , inhibitors . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
METHODS : Gene expression of SRC 1 , SRC 2 , SRC 3 , N CoR , SMRT , ERalpha , and PR was measured in 26 samples of normal endometrium and 30 primary endometrial carcinomas using real time RT PCR . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
The aim of the study was to test the hypothesis that expression of retinoid receptors ( RARalpha , RARbeta , RARgamma ) , rexinoid receptors ( RXRalpha , RXRbeta ) , thyroid hormone receptors ( TRalpha , TRbeta ) , estrogen receptors ( ERalpha , ERbeta ) , nuclear receptor coregulators ( N CoR , SRC 1 , SMRT ) , and in addition type 1 iodothyronine 5 ' deiodinase ( 5 ' DI ) , EGFR and erb B2 / neu would be different in mammary postlactating tissue in comparison with that of nonlactating mammary gland . ^^^ Using RT PCR , we have shown that expression of RARalpha , RXRalpha , TRalpha , ERalpha , ERbeta , N CoR , SRC 1 , SMRT and EGFR in rat was significantly increased in postlactating mammary gland when compared to that of nonlactating mammary tissue . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
We have found that estrogen markedly down regulates N CoR protein levels in estrogen receptor ( ER ) positive breast cancer cells without affecting N CoR mRNA levels , whereas levels of the related corepressor SMRT are unaffected . ^^^ This effect is attributable to estrogen up regulation of the ubiquitin ligase Siah 2 , which is a rapid and primary transcriptional response mediated by the ER , and precedes the loss of N CoR . ^^^ Our results illustrate a mechanism by which the estrogen ER complex markedly reduces the level of N CoR through a process involving the up regulation of Siah 2 and the subsequent targeting of N CoR for proteasomal degradation . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Scaffold attachment factors B 1 and B 2 ( SAFB1 / 2 ) and nuclear receptor corepressor ( N CoR ) function as ERalpha corepressors they directly interact with ERalpha , and repress transcription via repression domains . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
In human colorectal tissue samples , the gene expressions of 4 coactivators , p 300 , pCAF , TIF 2 and TRAP 220 , and 7 corepressors , N CoR , REA , MTA 1 , MTA1L1 , HDAC 1 , HDAC 2 and HDAC 3 , linked to estrogen receptors ( ER ) , were revealed by traditional RT PCR . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
TAB 2 acts as a sensor for inflammatory signals by serving as a molecular beacon for recruitment of MEKK 1 , which in turn mediates dismissal of the N CoR / HDAC complex and permits derepression of androgen and estrogen receptor target genes . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Following estradiol treatment of cells , chromatin immunoprecipitation analyses reveal recruitment of ER to the cyclin G 2 regulatory region , dismissal of RNA polymerase 2 , and recruitment of a complex containing N CoR and histone deacetylases , leading to a hypoacetylated chromatin state . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Yellow fluorescent protein ( YFP ) N CoR was distributed as intranuclear discrete dots , while coexpression of androgen receptor ( AR ) , glucocorticoid receptor alpha , and estrogen receptor alpha ligand dependently triggered redistribution of YFP N CoR . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
Three selected coactivator genes ( TIF 2 , AIB 1 , and GCN5L2 ) and two corepressor genes ( NCOR 1 and MTA1L1 ) were additionally investigated in a well characterized series of ERalpha positive unilateral invasive primary breast tumors from 99 postmenopausal patients who only received tamoxifen as adjuvant hormone therapy after primary surgery . ^^^ CONCLUSIONS : These findings point to NCOR 1 as a promising independent predictor of tamoxifen resistance in patients with ERalpha positive breast tumors . . ^^^ Expression analysis of estrogen receptor alpha coregulators in breast carcinoma : evidence that NCOR 1 expression is predictive of the response to tamoxifen . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
It was found that NCOR 1 mRNA was expressed at significantly higher levels in patients over 50 years of age , without axillary lymph node involvement , with tumor size less than 2 cm , with low or intermediate histological grade , with ERalpha / PgR positive and with HER 2 negative tumors . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
This review describes the roles of ( 1 ) hormone related factors ( ER , PgR , phosphorylated ER , ERbeta , aromatase ) , ( 2 ) growth related factors ( HER 2 , Ki 67 , p 53 ) , ( 3 ) ER cofactors ( AIB 1 , NcoR 1 ) , ( 4 ) estrogen dependent genes derived from gene expression profiling ( HDAC 6 , IGFBP4 / 5 ) , and ( 5 ) gene profiling using cDNA microarray . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
CONCLUSIONS : Increased NCoR 1 mRNA is a novel molecular lesion in breast cancer cells , which acts to suppress responsiveness of VDR target genes , resulting in 1alpha , 25 ( OH ) ( 2 ) D ( 3 ) resistance and seems to be particularly associated with estrogen receptor negativity . ^^^ |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: O75376 and P03372 |
Pubmed |
SVM Score :0.0 |
NA |
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