Differential Effects of Nuclear Receptor Corepressor (N-CoR) Expression Levels on Retinoic Acid Receptor-Mediated Repression Support the Existence of Dynamically Regulated Corepressor Complexes

Söderström, Mats; Vo, Annie P.; Heinzel, Thorsten; Lavinsky, Robert M.; Yang, Wenming; Seto, Edward; Peterson, Daniel A.; Rosenfeld, Michael G.; Glass, Christopher K.

doi:10.1210/mend.11.6.0018

Cited by 69 publications

(39 citation statements)

References 65 publications

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“…Lysates were separated on 10% SDS ± PAGE and Western blotted on immobilon-P membrane, detection using the 5C1 monoclonal antibody directed against the GAL4 DNA binding domain larger SMRT cDNA that is highly homologous to NCoR, has only recently been isolated (Ordentlich et al, 1999;Park et al, 1999). N-CoR and SMRT have been shown to be a component of large protein complexes that include histone deacetylase 1 and 2 Nagy et al, 1997) and Sin3A/B (Alland et al, 1997;Hassig et al, 1997;Soderstrom et al, 1997). The N-CoR corepressor is involved in repression by nuclear hormone receptors (Chen and Evans, 1995;Horlein et al, 1995) and Mad/Mxi-1 mediated repression, reviewed by (Schreiber and DePinho, 1998).…”

Section: Discussionmentioning

confidence: 99%

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

Masselink

Bernards

2000

Oncogene

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BS69 was ®rst identi®ed as a protein that interacts directly with the transactivation domain (conserved region 3) of the 289R adenovirus type 5 E1A protein.We show here that BS69 is a potent repressor of transcription. BS69 mediates repression, at least in part, through interaction with the co-repressor N-CoR. BS69 interacts with N-CoR through a MYND domain in its carboxyl terminus. A recently cloned splice variant of BS69, designated BRAM1, is also capable of interacting with N-CoR and E1A, but unlike BS69, is not able to repress transcription, indicating that N-CoR interaction is necessary but not su cient for BS69 repression. Expression of E1A inhibits repression mediated by BS69. Our data suggest that BS69 participates in transcriptional repressor complexes and that E1A can modulate these complexes through interaction with BS69. Oncogene (2000) 19, 1538 ± 1546.

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Section: Discussionmentioning

confidence: 99%

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

Masselink

Bernards

2000

Oncogene

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“…First, ETO may serve as a platform upon which distinct complexes assemble. For example, NCoR and SMRT are capable of interacting with Sin3, and this interaction could be facilitated by ETO (Li et al, 1997;Nagy et al, 1997;Soderstrom et al, 1997). Second, different complexes might associate with ETO in different cell types.…”

Section: Direct Interactions With Hdacsmentioning

confidence: 99%

ETO interacting proteins

Hug

Lazar

2004

Oncogene

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The 8;21 translocation produces a fusion between the ETO gene and that encoding the myeloid transcription factor AML1. The AML1-ETO fusion substitutes the majority of the ETO protein for the coregulator recruitment domains of AML1. Biochemical analyses of ETO have led to the identification of numerous interacting proteins including many corepressors. Importantly, the proteins interacting with ETO are different from those of wild-type AML1, suggesting that altered coregulator recruitment underlies the oncogenic properties of AML1-ETO. The list of corepressors capable of binding ETO includes histone deacetylases (HDACs) and components of distinct HDAC core complexes. These investigations have provided mechanistic insight into corepressor recruitment by ETO and clues to the leukemogenic activity of AML1-ETO.

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“…Endogenous N-CoR, BCL-6 and some other POZ domain containing proteins are found in the nucleus in a diuse microgranular fashion Reid et al, 1995;Soderstrom et al, 1997). Overexpression of these proteins by transient transfection appears to enlarge the granules to produce punctate structures (Bardwell and Treisman, 1994;Soderstrom et al, 1997).…”

Section: Subcellular Distribution Of N-cor and Bcl-6mentioning

confidence: 99%

“…Overexpression of these proteins by transient transfection appears to enlarge the granules to produce punctate structures (Bardwell and Treisman, 1994;Soderstrom et al, 1997). To test whether BCL-6 and N-CoR are found in the same granular and punctate nuclear structures, we performed immunouorescence on HeLa cells transiently transfected with BCL-6 and epitope-tagged N-CoR.…”

Section: Subcellular Distribution Of N-cor and Bcl-6mentioning

confidence: 99%

The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT

1998

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Virtually all diuse large cell lymphomas and a signi®cant fraction of follicular lymphomas contain translocations and/or point mutations in the 5' noncoding region of the putative oncogene BCL-6, that are presumed to deregulate its expression. BCL-6 encodes a Cys 2 -His 2 zinc ®nger transcriptional repressor with a POZ domain at its amino-terminus. The POZ (or BTB) domain, a 120-amino-acid motif, mediates homomeric and, in some proteins, heteromeric POZ-POZ interactions. In addition, the POZ domain is required for transcriptional repression of several proteins, including BCL-6. Using a yeast two-hybrid screen, we identi®ed N-CoR and SMRT as BCL-6 interacting proteins. Both N-CoR and SMRT, which were originally identi®ed as co-repressors for the unliganded nuclear thyroid hormone and retinoic acid receptors, are components of large complexes containing histone deacetylases. We show that the interaction between BCL-6 and these co-repressors is also detected in the more physiologically relevant mammalian two-hybrid assay. The POZ domain is necessary and sucient for interaction with these corepressors. BCL-6 and N-CoR co-localize to punctate regions of the nucleus. Furthermore, when BCL-6 is bound to its consensus recognition sequence in vivo, it can interact with N-CoR and SMRT. We ®nd, in vitro, that POZ domains from a variety of other POZ domaincontaining proteins, including the transcriptional repressor PLZF, as well as ZID, GAGA and a vaccinia virus protein, SalF17R, also interact with varying anities with N-CoR and SMRT. We ®nd that BCL-6 POZ domain mutations that disrupt the interaction with NCoR and SMRT no longer repress transcription. In addition, these mutations no longer self associate suggesting that self interaction is required for interaction with the co-repressors and for repression. More recently N-CoR has also been implicated in transcriptional repression by the Mad/Mxi proteins. Our demonstration that N-CoR and SMRT interact with the POZ domain containing proteins indicates that these co-repressors are likely involved in the mediation of repression by multiple classes of repressors and may explain, in part, how POZ domain containing repressors mediate transcriptional repression.

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Differential Effects of Nuclear Receptor Corepressor (N-CoR) Expression Levels on Retinoic Acid Receptor-Mediated Repression Support the Existence of Dynamically Regulated Corepressor Complexes

Cited by 69 publications

References 65 publications

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

ETO interacting proteins

The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT

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