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oai:docta.ucm.es:20.500.14352/136342024-09-11T12:38:44Zcom_20.500.14352_14col_20.500.14352_15

p38γ is essential for cell cycle progression and liver tumorigenesis Tomás Loba, Antonia Manieri, Elisa González Terán, Bárbara Mora, Alfonso Leiva Vega, Luis Santamans, Ayelén M. Romero-Becerra, Rafael Rodríguez, Elena Pintor Chocano, Aránzazu Feixas, Ferran López, Juan Antonio Caballero, Beatriz Trakala, Marianna Blanco, Óscar Torres, Jorge L. Hernández Cosido, Lourdes Montalvo Romeral, Valle Matesanz, Nuria Roche Molina, Marta Bernal, Juan Antonio Mischo, Hannah León, Marta Caballero, Ainoa Miranda-Saavedra, Diego Ruiz-Cabello Osuna, Jesús Nevzorova, Yulia Cubero Palero, Francisco Javier Bravo, Jerónima Vázquez, Jesús Malumbres, Marcos Marcos, Miguel Osuna, Silvia Sabio, Guadalupe 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. 2023-06-17T13:30:07Z 2023-06-17T13:30:07Z 2019-04-10 journal article Tomás Loba, A., Manieri, E., González terán, B. et al. «P38γ Is Essential for Cell Cycle Progression and Liver Tumorigenesis». Nature, vol. 568, n.o 7753, abril de 2019, pp. 557-60. DOI.org (Crossref), https://doi.org/10.1038/s41586-019-1112-8. 1476-4687 10.1038/s41586-019-1112-8 https://hdl.handle.net/20.500.14352/13634 https//doi.org/10.1038/s41586-019-1112-8 https://www.nature.com/articles/s41586-019-1112-8 eng MetAccembly (661160); NetMoDEzyme (679001) OBECAN (260464); DIREVENZYME (630978) (CTQ2014-59212-P), (SAF2017-87919R), (SAF2016-78711), (SAF2015-67077-R), (SAF2017-89901-R); (BIO2015-67580-P) IMMUNOTHERCAN-CM (S2010/BMD-2326); (B2017/BMD-3733); iLUNG (B2017/BMD-3884); EXOHEP-CM (S2017/BMD-3727) (SAF2016-79126-R; SAF2015-69920; SAF2014-61233-JIN) Consolider-Ingenio 2010 (SAF2014-57791-REDC); Excellence Network CellSYS (BFU2014-52125-REDT); (SAF2017-84494-C2-1-R) (SFB/TRR57/P04), (DFG NE 2128/2-1) Lilly European Diabetes Research Programme Dr Sabio 2017 Leonardo Grant for Researchers and Cultural Creators Investigadores-BBVA-2017 (IN[17]_BBM_BAS_0066) (RYC-2009-04972), (RYC-2014-15242), (RYC-2015-17438) (2018/117) (ProteoRed PRB3, IPT17/0019); (PI16/01548) CNIC program (SVP-2013-067639); (SEV-2015-0505) (HR17-00247) (GRS 1362/A/16); (INT/M/17/17); (GRS 1356/A/16); (GRS 1587/A/17) restricted access Nature Research