Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
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.
Laronga
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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.
Yang
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HY
Neal
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Lee
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MH
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005092:Exonucleases; D005095:Exoribonucleases; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011506:Proteins; D018844:Cyclin-Dependent Kinases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human