title: CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species.
abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H(2)O(2) decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H(2)O(2) increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H(2)O(2)-induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21(Cip1)/PCNA complex plays an important role as a regulator of cell fate decisions.
authors: Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305-806, Republic of Korea.
authors: Chae Young
authors: CY
authors: Hwang
authors: Seung-Min
authors: SM
authors: Lee
authors: Sung Sup
authors: SS
authors: Park
authors: Ki-Sun
authors: KS
authors: Kwon
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D011687:Purines; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051357:Cyclin-Dependent Kinase 2; C109140:CVT 313