title: Menin localization in cell membrane compartment.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: 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.|d Department of Urology , Renmin Hospital of Wuhan University , Wuhan 430060 , Hubei , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Department of Biology and Biotechnology , Shanghai Ocean University , 999 Hucheng Ring Rd Lingang New City, Shanghai , 201306 , China.
authors.forename: Jizhou
authors.initials: J
authors.lastname: Yan
authors.affiliation: c The Proteomics and Systems Facility, Department of Pharmacology, University of Pennsylvania Perelman School of Medicine , Philadelphia, 421 Curie Blvd., Philadelphia , PA 19104 , USA.
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Witze
authors.affiliation: 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.
authors.forename: Xianxin
authors.initials: X
authors.lastname: Hua
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D054878:Lipoylation; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C105373:MEN1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D011518:Proto-Oncogene Proteins; D012694:Serine
keywords: Cell membrane; menin; palmitoylation; secretory pathway