Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression |
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Authors: | Laronga C Yang H Y Neal C Lee M H |
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Institution: | Departments of Surgical Oncology/Molecular and Cellular Oncology and the Breast Cancer Research Program, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. |
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Abstract: | 14-3-3 sigma, implicated in cell cycle arrest by p53, was cloned by expression cloning through cyclin-dependent kinase 2 (CDK2) association. 14-3-3 sigma shares cyclin-CDK2 binding motifs with different cell cycle regulators, including p107, p130, p21(CIP1), p27(KIP1), and p57(KIP2), and is associated with cyclin.CDK complexes in vitro and in vivo. Overexpression of 14-3-3 sigma obstructs cell cycle entry by inhibiting cyclin-CDK activity in many breast cancer cell lines. Overexpression of 14-3-3 sigma can also inhibit cell proliferation and prevent anchorage-independent growth of these cell lines. These findings define 14-3-3 sigma as a negative regulator of the cell cycle progression and suggest that it has an important function in preventing breast tumor cell growth. |
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