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Publication : p38γ is essential for cell cycle progression and liver tumorigenesis.

First Author  Tomás-Loba A Year  2019
Journal  Nature Volume  568
Issue  7753 Pages  557-560
PubMed ID  30971822 Mgi Jnum  J:282878
Mgi Id  MGI:6384084 Doi  10.1038/s41586-019-1112-8
Citation  Tomas-Loba A, et al. (2019) p38gamma is essential for cell cycle progression and liver tumorigenesis. Nature 568(7753):557-560
abstractText  The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex(1). However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38gamma) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38gamma shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38gamma induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38gamma or treatment with the p38gamma inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38gamma, suggesting that p38gamma could be a therapeutic target in the treatment of this disease.
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