Identification and characterization of SAP25, a novel component of the mSin3 corepressor complex

Mol Cell Biol. 2006 Feb;26(4):1386-97. doi: 10.1128/MCB.26.4.1386-1397.2006.

Abstract

The transcriptional corepressor mSin3 is associated with histone deacetylases (HDACs) and is utilized by many DNA-binding transcriptional repressors. We have cloned and characterized a novel mSin3A-binding protein, SAP25. SAP25 binds to the PAH1 domain of mSin3A, associates with the mSin3A-HDAC complex in vivo, and represses transcription when tethered to DNA. SAP25 is required for mSin3A-mediated, but not N-CoR-mediated, repression. SAP25 is a nucleocytoplasmic shuttling protein, actively exported from the nucleus by a CRM1-dependent mechanism. A fraction of SAP25 is located in promyelocytic leukemia protein (PML) nuclear bodies, and PML induces a striking nuclear accumulation of SAP25. An isotope-coded affinity tag quantitative proteomic analysis of the SAP25 complex revealed that SAP25 is associated with several components of the mSin3 complex, nuclear export machinery, and regulators of transcription and cell cycle. These results suggest that SAP25 is a novel core component of the mSin3 corepressor complex whose subcellular location is regulated by PML.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • BALB 3T3 Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cloning, Molecular
  • HeLa Cells
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Rats
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sin3 Histone Deacetylase and Corepressor Complex

Substances

  • Carrier Proteins
  • Multiprotein Complexes
  • Repressor Proteins
  • SIN3A transcription factor
  • SAP25 protein, mouse
  • Histone Deacetylases
  • Sin3 Histone Deacetylase and Corepressor Complex