PMID- 28811300 OWN - NLM STAT- MEDLINE DCOM- 20180508 LR - 20181113 IS - 1479-6821 (Electronic) IS - 1351-0088 (Print) IS - 1351-0088 (Linking) VI - 24 IP - 10 DP - 2017 Oct TI - Epigenetic regulation by the menin pathway. PG - T147-T159 LID - 10.1530/ERC-17-0298 [doi] AB - There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of menin in epigenetic regulation of gene transcription and cell signaling, as well as posttranslational regulation of menin itself. In particular, we will review the progress in studying structural and functional interactions of menin with various histone modifiers and transcription factors such as MLL, PRMT5, SUV39H1 and other transcription factors including c-Myb and JunD. Moreover, the role of menin in regulating cell signaling pathways such as TGF-beta, Wnt and Hedgehog, as well as miRNA biogenesis and processing will be described. Further, the regulation of the MEN1 gene transcription, posttranslational modifications and stability of menin protein will be reviewed. These various modes of regulation by menin as well as regulation of menin by various biological factors broaden the view regarding how menin controls various biological processes in neuroendocrine organ homeostasis. CI - (c) 2017 Society for Endocrinology. FAU - Feng, Zijie AU - Feng Z AD - Department of Cancer BiologyAbramson Family Cancer Research Institute, Abramson Cancer Center, Institute of Diabetes, Obesity, and Metabolism (IDOM), University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Ma, Jian AU - Ma J AD - Department of Cancer BiologyAbramson Family Cancer Research Institute, Abramson Cancer Center, Institute of Diabetes, Obesity, and Metabolism (IDOM), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - State Key Laboratory of Veterinary BiotechnologyHarbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - Hua, Xianxin AU - Hua X AD - Department of Cancer BiologyAbramson Family Cancer Research Institute, Abramson Cancer Center, Institute of Diabetes, Obesity, and Metabolism (IDOM), University of Pennsylvania, Philadelphia, Pennsylvania, USA huax@mail.med.upenn.edu. LA - eng GR - R01 CA178856/CA/NCI NIH HHS/United States GR - R01 DK097555/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20170815 PL - England TA - Endocr Relat Cancer JT - Endocrine-related cancer JID - 9436481 RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) SB - IM MH - Epigenesis, Genetic/*genetics MH - Humans MH - Neuroendocrine Tumors/*genetics/metabolism MH - Proto-Oncogene Proteins/*genetics/metabolism PMC - PMC5612327 MID - NIHMS904607 OTO - NOTNLM OT - MEN1 OT - epigenetic regulation OT - menin OT - neuroendocrine tumor COIS- Declaration of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review. EDAT- 2017/08/16 06:00 MHDA- 2018/05/09 06:00 PMCR- 2018/10/01 CRDT- 2017/08/17 06:00 PHST- 2017/08/09 00:00 [received] PHST- 2017/08/15 00:00 [accepted] PHST- 2017/08/16 06:00 [pubmed] PHST- 2018/05/09 06:00 [medline] PHST- 2017/08/17 06:00 [entrez] PHST- 2018/10/01 00:00 [pmc-release] AID - ERC-17-0298 [pii] AID - 10.1530/ERC-17-0298 [doi] PST - ppublish SO - Endocr Relat Cancer. 2017 Oct;24(10):T147-T159. doi: 10.1530/ERC-17-0298. Epub 2017 Aug 15.