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

Anatoly Y Nikolaev; Nikolaos A Papanikolaou; Muyang Li; Jun Qin; Wei Gu

doi:10.1016/j.bbrc.2004.08.227

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.

Authors

Anatoly Y Nikolaev¹, Nikolaos A Papanikolaou, Muyang Li, Jun Qin, Wei Gu

Affiliation

¹ Department of Pathology, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

PMID: 15451426
DOI: 10.1016/j.bbrc.2004.08.227

Abstract

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

Substances

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