1. Brap2 Functions as a Cytoplasmic Retention Protein for p21 during Monocyte Differentiation
- Author
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Hidenori Suzuki, Shin Enosawa, Seiichi Suzuki, Shuki Mizutani, Minoru Asada, Kazuhiro Ohmi, Domenico Delia, and Akira Yuo
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,Cytoplasm ,Ubiquitin-Protein Ligases ,Cellular differentiation ,Nuclear Localization Signals ,Apoptosis ,HL-60 Cells ,Biology ,Transfection ,Monocytes ,Cell Line ,Downregulation and upregulation ,Cyclins ,Humans ,NLS ,RNA, Messenger ,RNA, Small Interfering ,Cell Growth and Development ,Molecular Biology ,Binding Sites ,Base Sequence ,U937 cell ,Cell Differentiation ,U937 Cells ,Cell Biology ,Cell cycle ,Molecular biology ,Recombinant Proteins ,Cell biology ,Monocyte differentiation ,Carrier Proteins ,Nuclear localization sequence ,HeLa Cells ,Subcellular Fractions - 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.
- Published
- 2004
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