2026-04-29T22:51:36Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/260882025-12-18T12:55:52Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571
Repisalud
author
Lafarga, Vanesa
author
Cuadrado, Ana
author
Lopez de Silanes, Isabel
author
Bengoechea, Rocio
author
Fernandez-Capetillo, Oscar
author
Nebreda, Angel R
funder
Fundacion Cientifica de la AECC
funder
MINISTERIO DE CIENCIA E INNOVACIÓN (ESPAÑA)
funder
Instituto de Salud Carlos III
2025-01-21T12:34:28Z
2025-01-21T12:34:28Z
2009-08
Mol Cell Biol . 2009 Aug;29(16):4341-51
Mol Cell Biol
19528229
https://hdl.handle.net/20.500.12105/26088
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.
eng
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.
research article
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URL
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File
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application/pdf
p38mitogenactivated-2009.pdf