| Literature DB >> 30971822 |
Elisa Manieri1,2, Bárbara González-Terán1, Antonia Tomás-Loba1, Alfonso Mora1, Luis Leiva-Vega1, Ayelén M Santamans1, Rafael Romero-Becerra1, Elena Rodríguez1, Aránzazu Pintor-Chocano1, Ferran Feixas3, Juan Antonio López1, Beatriz Caballero1, Marianna Trakala4, Óscar Blanco5, Jorge L Torres5, Lourdes Hernández-Cosido5, Valle Montalvo-Romeral1, Nuria Matesanz1, Marta Roche-Molina1, Juan Antonio Bernal1, Hannah Mischo6, Marta León1, Ainoa Caballero1, Diego Miranda-Saavedra7,8, Jesús Ruiz-Cabello1,9,10,11,12, Yulia A Nevzorova13,12, Francisco Javier Cubero14,15, Jerónimo Bravo16, Jesús Vázquez1,17, Marcos Malumbres4, Miguel Marcos5, Sílvia Osuna3,18, Guadalupe Sabio19.
Abstract
The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.Entities:
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Year: 2019 PMID： 30971822 DOI： 10.1038/s41586-019-1112-8
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962