Pim-2 phosphorylation of p21Cip1/WAF1 enhances its stability and inhibits cell proliferation in HCT116 cells |
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| Authors: | Zeping Wang Yandong Zhang Juan Jenny Gu Christine Davitt Raymond Reeves Nancy S Magnuson |
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| Institution: | 1. School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA;2. Franceschi Microscopy Imaging Center, Washington State University, Pullman, WA 99164-4210, USA;1. Department of Electrical and Computer Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA;2. National Research Council, Ottawa, ON, Canada KIA 0R6;1. Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;2. Department of Oncology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;3. Department of Molecular Structure and Characterization, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;4. Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;5. Department of Discovery Technologies, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;6. Department of Pharmaceutics R&D, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;1. Terry Fox Lab, British Columbia Cancer Agency, Vancouver, BC, Canada;2. The University of British Columbia, Vancouver, BC, Canada;1. Paediatric Intensive Care Unit at the Department of Paediatrics, Reina Sofia University Hospital, University of Córdoba, Spain;2. Paediatric Research Unit at Reina Sofía University Hospital, Maimónides Biomedical Research Institute of Córdoba (IMIBIC), University of Cordoba, Spain;3. Pediatric Cardiovascular Surgery Unit, Reina Sofia University Hospital, Spain;4. Paediatric Cardiology Unit at the Department of Paediatrics, Reina Sofia University Hospital, Spain;1. UNIVERSITY OF CALGARY |
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| Abstract: | Pim-2 kinase is one of the three highly conserved Pim family members which are known to be involved in cell survival and cell proliferation. Here we demonstrate that like Pim-1, Pim-2 also phosphorylates the cell cycle inhibitor p21Cip1/WAF1 (p21) on Thr145 in vitro and in vivo. Overexpression of Pim-2 in HCT116 cells leads to the increased stability of p21 and results in enhanced levels of both exogenous and endogenous p21 proteins. Knockdown of Pim-2 expression via siRNA results in reduced level of endogenous p21, indicating that like Pim-1, Pim-2 is another legitimate p21 kinase. However, Pim-2 has no influence on the nuclear localization of p21 in HCT116 cells. In addition, Pim-2 is able to arrest the cell cycle at G1/S phase and inhibit cell proliferation through phosphorylation of p21 in HCT116 cells. These data suggest that Pim-2 phosphorylation of p21 enhances p21's stability and inhibits cell proliferation in HCT116 cells. |
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