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oai:repisalud.isciii.es:20.500.12105/260882025-12-18T12:55:52Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Lafarga, Vanesa author Cuadrado, Ana author Lopez de Silanes, Isabel author Bengoechea, Rocio author Fernandez-Capetillo, Oscar author Nebreda, Angel R author 2009-08 Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G(2)/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G(1)/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21(Cip1) is thought to make a major contribution to the G(1)/S cell cycle arrest induced by gamma radiation. We show here that inhibition of p38 MAPK impairs p21(Cip1) accumulation and, as a result, the ability of cells to arrest in G(1) in response to gamma radiation. We found that p38 MAPK induces p21(Cip1) mRNA stabilization, without affecting its transcription or the stability of the protein. In particular, p38 MAPK phosphorylates the mRNA binding protein HuR on Thr118, which results in cytoplasmic accumulation of HuR and its enhanced binding to the p21(Cip1) mRNA. Our findings help to understand the emerging role of p38 MAPK in the cellular responses to DNA damage and reveal the existence of p53-independent networks that cooperate in modulating p21(Cip1) levels at the G(1)/S checkpoint. Mol Cell Biol . 2009 Aug;29(16):4341-51 Mol Cell Biol 19528229 https://hdl.handle.net/20.500.12105/26088 DNA-DAMAGE P21(WAF1/CIP1) EXPRESSION DIFFERENTIAL ACTIVATION ATAXIA-TELANGIECTASIA UV-IRRADIATION S-PHASE PHOSPHORYLATION p53 CELLS INSTABILITY p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.