Identification of a novel BRMS1-homologue protein p40 as a component of the mSin3A/p33(ING1b)/HDAC1 deacetylase complex

Biochem Biophys Res Commun. 2004 Oct 29;323(4):1216-22. doi: 10.1016/j.bbrc.2004.08.227.


Repression of gene transcription is mediated by histone deacetylases containing repressor-co-repressor complexes, which are recruited to promoters of target genes via interactions with sequence-specific transcription factors. The mammalian Sin3A co-repressor complex contains a core of at least seven proteins including the pRb-interacting protein RBP1 and a putative tumor suppressor p33(ING1b). By biochemical purification and mass spectrometry, we have identified a novel component p40 from this complex. p40 bears homology to both yeast Sds3, a component of yeast histone deacetylase complexes, and its mammalian homologue mSds3. The p40-associated complex purified from human cells shows a strong histone deacetylase activity. When tethered to a Gal-DNA binding domain, the Gal-p40 is able to significantly repress transcription of a Gal-luciferase promoter. Interestingly, database analysis reveals that p40 is also highly homologous to BRMS1, a breast carcinoma metastasis suppressor, and overexpression of p40 in human cells can significantly inhibit cell growth. Thus, our data indicate that p40 may be critically involved in transcription repression of cell growth-associated gene expression by recruiting the HDAC1 deacetylase complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • DNA-Binding Proteins
  • Enzyme Activation
  • Genes, Tumor Suppressor
  • Histone Deacetylase 1
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans
  • Inhibitor of Growth Protein 1
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Structure-Activity Relationship
  • Tumor Suppressor Proteins


  • BRMS1 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • ING1 protein, human
  • Inhibitor of Growth Protein 1
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • SIN3A transcription factor
  • Tumor Suppressor Proteins
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Sin3 Histone Deacetylase and Corepressor Complex