p38γ is essential for cell cycle progression and liver tumorigenesis
Antonia Tomás-Loba1, Elisa Manieri1,2, Bárbara González-Terán1
1Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Nature
|April 12, 2019
Summary
p38 MAPK gamma (p38γ) acts as a CDK-like kinase, regulating cell cycle entry. Inhibiting p38γ in mice reduced liver tumor formation, and high p38γ expression in human liver cancer suggests it as a therapeutic target.
Area of Science:
- Cell Biology
- Molecular Oncology
Background:
- The cell cycle is regulated by cyclin-dependent kinases (CDKs), but the G0-to-G1 transition mechanism remains unclear.
- CDKs are crucial for cell cycle progression, making their regulatory pathways key targets for cancer research.
Purpose of the Study:
- To investigate the role of p38 MAPK gamma (p38γ) in cell cycle regulation, specifically the G0-to-G1 transition.
- To determine if p38γ could serve as a therapeutic target for hepatocellular carcinoma.
Main Methods:
- Comparative analysis of p38γ and CDK family members based on sequence homology, inhibition sensitivity, and substrate specificity.
- In vivo studies using mouse hepatocytes to assess p38γ's role in proliferation and liver tumor formation.
- Analysis of human hepatocellular carcinoma biopsies for p38γ expression levels.
Main Results:
- p38γ functions as a CDK-like kinase, cooperating with CDKs to control cell cycle entry.
- p38γ promotes hepatocyte proliferation by phosphorylating the retinoblastoma tumor suppressor protein.
- Inhibition of p38γ or its absence protected against chemically induced liver tumors in mice.
- Human hepatocellular carcinoma samples exhibit elevated p38γ expression.
Conclusions:
- p38γ plays a significant role in regulating the G0-to-G1 cell cycle transition and liver proliferation.
- p38γ is implicated in liver tumorigenesis and represents a potential therapeutic target for hepatocellular carcinoma.
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