Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription.
Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple human and murine cancer cells without inhibiting tumorigenicity. By yeast two-hybrid and co-immunoprecipitation, BRMS1 interacts with retinoblastoma binding protein 1 and at least seven members of the mSin3 histone deacetylase (HDAC) complex in human breast and melanoma cell lines. BRMS1 co-immunoprecipitates enzymatically active HDAC proteins and represses transcription when recruited to a Gal4 promoter in vivo. BRMS1 exists in large mSin3 complex(es) of approximately 1.4-1.9 MDa, but also forms smaller complexes with HDAC1. Deletion analyses show that the carboxyl-terminal 42 amino acids of BRMS1 are not critical for interaction with much of the mSin3 complex and that BRMS1 appears to have more than one binding point to the complex. These results further show that BRMS1 may participate in transcriptional regulation via interaction with the mSin3.HDAC complex and suggest a novel mechanism by which BRMS1 might suppress cancer metastasis.
Meehan
William J
WJ
Department of Pathology, Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-0850, USA.
Samant
Rajeev S
RS
Hopper
James E
JE
Carrozza
Michael J
MJ
Shevde
Lalita A
LA
Workman
Jerry L
JL
Eckert
Kristin A
KA
Verderame
Michael F
MF
Welch
Danny R
DR
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
C533431:Arid4a protein, mouse; C410024:BRMS1 protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex