Hwang, Chae Young Lee, Cheolju Kwon, Ki-Sun 2024-01-20T21:05:27Z 2024-01-20T21:05:27Z 2021-09-03 2009-06-15 0270-7306 https://pubs.kist.re.kr/handle/201004/132393 p21(Cip1) is an inhibitor of cell cycle progression that promotes G(1)-phase arrest by direct binding to cycl-independent kinase and proliferating cell nuclear antigen. Here we demonstrate that mitogenic stimuli, such as epidermal growth factor treatment and oncogenic Ras transformation, induce p21(Cip1) downregulation at the posttranslational level. This downregulation requires the sustained activation of extracellular signal-regulated kinase 2 (ERK2), which directly interacts with and phosphorylates p21(Cip1), promoting p21(Cip1) nucleocytoplasmic translocation and ubiquitin-dependent degradation, thereby resulting in cell cycle progression. ERK1 is not likely involved in this process. Phosphopeptide analysis of in vitro ERK2-phosphorylated p21(Cip1) revealed two phosphorylation sites, Thr57 and Ser130. Double mutation of these sites abolished ERK2-mediated p21(Cip1) translocation and degradation, thereby impairing ERK2-dependent cell cycle progression at the G(1)/S transition. These results indicate that ERK2 activation transduces mitogenic signals, at least in part, by downregulating the cell cycle inhibitory protein p21(Cip1). English AMER SOC MICROBIOLOGY ACTIVATED PROTEIN-KINASE CYCLIN-DEPENDENT KINASES CDK INHIBITORS UV-IRRADIATION PCNA BINDING MAP KINASE S-PHASE P21 PROTEASOME P21(WAF1/CIP1) Extracellular Signal-Regulated Kinase 2-Dependent Phosphorylation Induces Cytoplasmic Localization and Degradation of p21(Cip1) Article 10.1128/MCB.01758-08 1 MOLECULAR AND CELLULAR BIOLOGY, v.29, no.12, pp.3379 - 3389 MOLECULAR AND CELLULAR BIOLOGY 29 12 3379 3389 scie scopus 000266436300013 2-s2.0-67649205804 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article ACTIVATED PROTEIN-KINASE CYCLIN-DEPENDENT KINASES CDK INHIBITORS UV-IRRADIATION PCNA BINDING MAP KINASE S-PHASE P21 PROTEASOME P21(WAF1/CIP1)