PMID- 26560942 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20200930 IS - 1555-8576 (Electronic) IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 17 IP - 1 DP - 2016 TI - Menin localization in cell membrane compartment. PG - 114-22 LID - 10.1080/15384047.2015.1108497 [doi] AB - Menin is encoded by the MEN1 gene, which is mutated in an inherited human syndrome, multiple endocrine neoplasia type 1(MEN1). Menin is primarily nuclear protein, acting as a tumor suppressor in endocrine organs, but as an oncogenic factor in the mixed lineage leukemia, in a tissue-specific manner. Recently, the crystal structures of menin with different binding partners reveal menin as a key scaffold protein that functionally interacts with various partners to regulate gene transcription in the nucleus. However, outside the nucleus, menin also regulates multiple signaling pathways that traverse the cell surface membrane. The precise nature regarding to how menin associates with the membrane fraction is poorly understood. Here we show that a small fraction of menin associates with the cell membrane fraction likely via serine palmitoylation. Moreover, the majority of the membrane-associated menin may reside inside membrane vesicles, as menin is protected from trypsin-mediated proteolysis, but disruption of the membrane fraction using detergent abolishes the detection. Consistently, cellular staining for menin also reveals the distribution of menin in the cell membrane and the punctate-like cell organelles. Our findings suggest that part of intracellular menin associates with the cell membrane peripherally as well as resides within the membrane vesicles. FAU - He, Xin AU - He X AD - a Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine , 421 Curie Blvd., Philadelphia , PA 19104 , USA. FAU - Wang, Lei AU - Wang L AD - a Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine , 421 Curie Blvd., Philadelphia , PA 19104 , USA. AD - d Department of Urology , Renmin Hospital of Wuhan University , Wuhan 430060 , Hubei , China. FAU - Yan, Jizhou AU - Yan J AD - b Department of Biology and Biotechnology , Shanghai Ocean University , 999 Hucheng Ring Rd Lingang New City, Shanghai , 201306 , China. FAU - Yuan, Chaoxing AU - Yuan C AD - c The Proteomics and Systems Facility, Department of Pharmacology, University of Pennsylvania Perelman School of Medicine , Philadelphia, 421 Curie Blvd., Philadelphia , PA 19104 , USA. FAU - Witze, Eric S AU - Witze ES AD - a Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine , 421 Curie Blvd., Philadelphia , PA 19104 , USA. FAU - Hua, Xianxin AU - Hua X AD - a Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine , 421 Curie Blvd., Philadelphia , PA 19104 , USA. LA - eng GR - 1-R01-CA-178856/CA/NCI NIH HHS/United States GR - R01-DK085121/DK/NIDDK NIH HHS/United States GR - R01 DK097555/DK/NIDDK NIH HHS/United States GR - R01 CA178856/CA/NCI NIH HHS/United States GR - P30DK050306/DK/NIDDK 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 - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (MEN1 protein, human) RN - 0 (Nuclear Matrix-Associated Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 452VLY9402 (Serine) SB - IM MH - Animals MH - Cell Membrane/genetics/*metabolism MH - Cell Nucleus/genetics/*metabolism MH - Crystallography, X-Ray MH - Humans MH - Lipoylation MH - Mice MH - Nuclear Matrix-Associated Proteins/chemistry/genetics MH - Proto-Oncogene Proteins/chemistry/genetics/*metabolism MH - Rats MH - Serine/metabolism MH - Signal Transduction/genetics PMC - PMC4847924 OTO - NOTNLM OT - Cell membrane OT - menin OT - palmitoylation OT - secretory pathway EDAT- 2015/11/13 06:00 MHDA- 2016/11/01 06:00 PMCR- 2016/11/11 CRDT- 2015/11/13 06:00 PHST- 2015/11/13 06:00 [entrez] PHST- 2015/11/13 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2016/11/11 00:00 [pmc-release] AID - 1108497 [pii] AID - 10.1080/15384047.2015.1108497 [doi] PST - ppublish SO - Cancer Biol Ther. 2016;17(1):114-22. doi: 10.1080/15384047.2015.1108497.