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Laronga, C, Yang, HY, Neal, C and Lee, MH (2000) Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J. Biol. Chem. 275:23106-12
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.
14-3-3 Proteins; Amino Acid Sequence; Animals; Breast Neoplasms/pathology; Cell Adhesion/genetics; Cell Cycle; Cell Division/genetics; Cell Nucleus/enzymology; Cloning, Molecular; Cyclin-Dependent Kinases/antagonists & inhibitors; Cyclin-Dependent Kinases/metabolism; Enzyme Inhibitors/metabolism; Exonucleases; Humans; Mice; Molecular Sequence Data; Neoplasm Proteins; Protein Binding; Proteins/chemistry; Proteins/genetics; Proteins/metabolism; Tumor Cells, Cultured; Tumor Markers, Biological
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