title: Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation.
abstract: The cell cycle inhibitor p21 plays an important role in monocytic cell differentiation, during which it translocates from the nucleus to cytoplasm. This process involves the negative regulation of the p21 nuclear localization signal (NLS). Here, we sought to determine the relationship between the cytoplasmic translocation of p21 and another molecule, Brap2, a cytoplasmic protein which binds the NLS of BRCA1 and was recently reported to inactivate KSR in the Ras-activating signal pathway under the name of IMP. We report that p21 and Brap2 directly interact, both in vitro and in vivo, in a manner requiring the NLS of p21 and the C-terminal portion of Brap2. When it is cotransfected with Brap2, p21 is expressed in the cytoplasm. Monocytic differentiation of the promyelomonocytic cell lines U937 and HL60 is associated with the upregulation of Brap2 expression concomitantly with the upregulation and cytoplasmic relocalization of p21. Our results underscore the role played by Brap2 in the process of cytoplasmic translocation of p21 during monocyte differentiation.
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Asada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ohmi
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.forename: Shin
authors.initials: S
authors.lastname: Enosawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Yuo
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D019913:Nuclear Localization Signals; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells; D044767:Ubiquitin-Protein Ligases
chemical_list: C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019913:Nuclear Localization Signals; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases