PMID- 31211356 OWN - NLM STAT- MEDLINE DCOM- 20191206 LR - 20240214 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 160 IP - 8 DP - 2019 Aug 1 TI - Menin Associates With the Mitotic Spindle and Is Important for Cell Division. PG - 1926-1936 LID - 10.1210/en.2019-00274 [doi] AB - Menin is the protein mutated in patients with multiple endocrine neoplasia type 1 (MEN1) syndrome and their corresponding sporadic tumor counterparts. We have found that menin functions in promoting proper cell division. Here, we show that menin localizes to the mitotic spindle poles and the mitotic spindle during early mitosis and to the intercellular bridge microtubules during cytokinesis in HeLa cells. In our study, menin depletion led to defects in spindle assembly and chromosome congression during early mitosis, lagging chromosomes during anaphase, defective cytokinesis, multinucleated interphase cells, and cell death. In addition, pharmacological inhibition of the menin-MLL1 interaction also led to similar cell division defects. These results indicate that menin and the menin-MLL1 interaction are important for proper cell division. These results highlight a function for menin in cell division and aid our understanding of how mutation and misregulation of menin promotes tumorigenesis. CI - Copyright (c) 2019 Endocrine Society. FAU - Sawicki, Mark P AU - Sawicki MP AD - Department of Surgery, VA Greater Los Angeles Healthcare System, Los Angeles, California. AD - Department of Surgery, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, California. AD - Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California. FAU - Gholkar, Ankur A AU - Gholkar AA AD - Department of Chemistry and Biochemistry, University of California, Los Angeles, California. FAU - Torres, Jorge Z AU - Torres JZ AD - Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California. AD - Department of Chemistry and Biochemistry, University of California, Los Angeles, California. AD - Molecular Biology Institute, University of California, Los Angeles, California. LA - eng GR - T32 GM007185/GM/NIGMS NIH HHS/United States GR - UL1 TR001881/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (KMT2A protein, human) RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) SB - IM MH - *Cell Division MH - HCT116 Cells MH - HeLa Cells MH - Histone-Lysine N-Methyltransferase/physiology MH - Humans MH - Myeloid-Lymphoid Leukemia Protein/physiology MH - Proto-Oncogene Proteins/genetics/*physiology MH - Spindle Apparatus/*physiology PMC - PMC6656424 EDAT- 2019/06/19 06:00 MHDA- 2019/12/18 06:00 PMCR- 2020/06/18 CRDT- 2019/06/19 06:00 PHST- 2019/04/04 00:00 [received] PHST- 2019/06/11 00:00 [accepted] PHST- 2019/06/19 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/06/19 06:00 [entrez] PHST- 2020/06/18 00:00 [pmc-release] AID - 5519300 [pii] AID - 201900274 [pii] AID - 10.1210/en.2019-00274 [doi] PST - ppublish SO - Endocrinology. 2019 Aug 1;160(8):1926-1936. doi: 10.1210/en.2019-00274.