Characterization of Receptor Interaction and Transcriptional Repression by the Corepressor SMRT
SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) are two related transcriptional corepressors that contain separable domains capable of interacting with unliganded nuclear receptors and repressing basal transcription. To decipher the me...
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Veröffentlicht in: | Molecular endocrinology (Baltimore, Md.) Md.), 1997-12, Vol.11 (13), p.2025-2037 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | SMRT (silencing mediator of retinoic acid and
thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) are
two related transcriptional corepressors that contain separable domains
capable of interacting with unliganded nuclear receptors and repressing
basal transcription. To decipher the mechanisms of receptor interaction
and transcriptional repression by SMRT/N-CoR, we have characterized
protein-protein interacting surfaces between SMRT and nuclear receptors
and defined transcriptional repression domains of both SMRT and N-CoR.
Deletional analysis reveals two individual nuclear receptor domains
necessary for stable association with SMRT and a C-terminal helix
essential for corepressor dissociation. Coordinately, two SMRT domains
are found to interact independently with the receptors. Functional
analysis reveals that SMRT contains two distinct repression domains,
and the corresponding regions in N-CoR also repress basal
transcription. Both repression domains in SMRT and N-CoR interact
weakly with mSin3A, which in turn associates with a histone deacetylase
HDAC1 in a mammalian two-hybrid assay. Far-Western analysis
demonstrates a direct protein-protein interaction between two N-CoR
repression domains with mSin3A. Finally we demonstrate that
overexpression of full-length SMRT further represses basal
transcription from natural promoters. Together, these results support a
role of SMRT/N-CoR in corepression through the utilization of multiple
mechanisms for receptor interactions and transcriptional repression. |
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ISSN: | 0888-8809 1944-9917 |
DOI: | 10.1210/mend.11.13.0028 |