Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-κB, and serum response factor

Soo Kyung Lee, Jung Hyun Kim, Young Chul Lee, Jae Hun Cheong, Jae Woon Lee

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is known to interact with Sin3 and recruit the histone deacetylases (HDACs) that lead to hypoacetylation of histones and transrepression of target transcription factors. Herein, we found that coexpression of SMRT significantly repressed transactivations by activating protein-1 (AP-1), nuclear factor-κB (NFκB), and serum response factor (SRF) in a dose- dependent manner, but not in the presence of trichostatin A, a specific inhibitor of HDAC. Similarly, coexpression of HDAC1 and mSin3A also showed repressive effects. Consistent with these results, the C-terminal region of SMRT directly interacted with SRF, the AP-1 components c-Jun and c-Fos, and the NFκB components p50 and p65, as demonstrated by the yeast and mammalian two hybrid tests as well as the glutathione S-transferase pull down assays. Thus, we concluded that SMRT serves to recruit Sin3/HDACs to SRF, NFκB, and AP-1 in vivo and modulate their transactivation.

Original languageEnglish (US)
Pages (from-to)12470-12474
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number17
DOIs
StatePublished - Apr 28 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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