Regulation of SMRT corepressor dimerization and composition by MAP kinase phosphorylation

Natalia Varlakhanova, Johnnie B. Hahm, Martin L. Privalsky

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptors) corepressor mediates gene repression by nuclear receptors and other transcriptional factors. The SMRT protein serves as a key nucleating core that organizes the assembly of a larger corepressor complex. We report here that SMRT interacts with itself to form a protein dimer, and that Erk2, a mitogen-activated protein (MAP) kinase, disrupts this SMRT self-dimerization in vitro and in vivo. Notably Erk2 phosphorylation also results in a re-organization of the overall corepressor complex, characterized by a reduced sedimentation coefficient, partial release of HDAC3, TBL-1, and TBLR-1, and inhibition of transcriptional repression. We propose that SMRT dimers form the central platform on which additional corepressor components assemble, and that kinase signaling modifies the architecture, composition, and function of this complex. These observations contribute to our understanding of how the SMRT corepressor complex assembles and is regulated during cell proliferation and differentiation.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume332
Issue number1-2
DOIs
StatePublished - Jan 30 2011

Keywords

  • Corepressor complex
  • Dimer
  • Erk
  • MAP kinases
  • SMRT

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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