Menin是一种肿瘤抑制因子，它通过与mSin3A-组蛋白去乙酰化酶复合物结合来抑制JunD介导的转录活性。

Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex.

作者信息

Kim Hyungsoo, Lee Ji-Eun, Cho Eun-Jung, Liu Jun O, Youn Hong-Duk

机构信息

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.

出版信息

Cancer Res. 2003 Oct 1;63(19):6135-9.

PMID:14559791

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.

摘要

Menin是I型多发性内分泌肿瘤（MEN1）的基因产物，已知其作为肿瘤抑制因子可抑制JunD转录因子。然而，Menin抑制JunD转录活性的机制仍不清楚。在本研究中，我们发现Menin通过以mSin3A依赖的方式募集组蛋白去乙酰化酶，作为JunD转录活性的共抑制因子。氨基酸搜索显示，Menin的中央结构域包含一个α-螺旋mSin3相互作用结构域[SID（371-387）]。Menin的SID突变（L381P/A385P）消除了mSin3A与Menin的配对两亲螺旋2结构域之间的相互作用，并降低了其抑制JunD转录活性的能力，这表明Menin的SID对于募集mSin3A-组蛋白去乙酰化酶复合物以抑制JunD转录活性很重要。