title: Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex.
abstract: Menin, a gene product of multiple endocrine neoplasia type I (MEN1), is known to act as a tumor suppressor to repress JunD transcription factor. However, the mechanism by which Menin represses JunD transcriptional activity was still unclear. In this study, we found that Menin is a corepressor against JunD transcriptional activity via recruitment of histone deacetylases in an mSin3A-dependent manner. The amino acid search revealed that central domain of Menin includes a alpha-helical mSin3-interacting domain [SID (371-387)]. The SID mutation of Menin (L381P/A385P) abolished the interaction between mSin3A and paired amphipathic helix 2 domain of Menin and reduced its ability to repress JunD transcriptional activity, implicating that SID of Menin is important for recruiting an mSin3A-histone deacetylase complex to repress JunD transcriptional activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Republic of Korea.
authors.forename: Hyungsoo
authors.initials: H
authors.lastname: Kim
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Jun O
authors.initials: JO
authors.lastname: Liu
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D000595:Amino Acid Sequence; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex