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p38γ is essential for cell cycle progression and liver tumorigenesis

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Tomás-Loba, Antonia and Manieri, Elisa and González-Terán, Bárbara and Mora, Alfonso and Leiva-Vega, Luis and Santamans, Ayelén M. and Romero-Becerra, Rafael and Rodríguez, Elena and Pintor-Chocano, Aránzazu and Feixas, Ferran and López, Juan Antonio and Caballero, Beatriz and Trakala, Marianna and Blanco, Óscar and Torres, Jorge L. and Hernández-Cosido, Lourdes and Montalvo-Romeral, Valle and Matesanz, Nuria and Roche-Molina, Marta and Bernal, Juan Antonio and Mischo, Hannah and León, Marta and Caballero, Ainoa and Miranda-Saavedra, Diego and Ruiz-Cabello, Jesús and Nevzorova, Yulia A. and Cubero, Francisco Javier and Bravo, Jerónima and Vázquez, Jesús and Malumbres, Marcos and Marcos, Miguel and Osuna, Silvia and Sabio, Guadalupe (2019) p38γ is essential for cell cycle progression and liver tumorigenesis. Nature, 568 . pp. 557-560. ISSN 1476-4687

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Official URL: https://www.nature.com/articles/s41586-019-1112-8



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.


Item Type:Article
Uncontrolled Keywords:Cell-cycle exit, Kinases, Phosphorylation, Targeted therapies
Subjects:Medical sciences > Medicine > Gastroenterology and Hepatology
Medical sciences > Medicine > Oncology
Medical sciences > Biology > Genetics
ID Code:57170
Deposited On:01 Oct 2019 15:18
Last Modified:02 Oct 2019 07:49

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