Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex.
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.
Kim
Hyungsoo
H
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.
Lee
Ji-Eun
JE
Cho
Eun-Jung
EJ
Liu
Jun O
JO
Youn
Hong-Duk
HD
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
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