title: p38alpha: a suppressor of cell proliferation and tumorigenesis.
abstract: The mitogen-activated protein kinase (MAPK) p38alpha is involved in numerous biological processes and is a drug target for inflammation-associated diseases. Genetic analysis in mice demonstrated that fetuses lacking p38alpha are embryonic lethal owing to impaired placental development. The function of p38alpha in mice after birth remained unclear until conditional alleles of p38alpha were used. It was found that p38alpha is essential for lung function in both neonatal and adult mice. Increased proliferation and impaired differentiation are the hallmarks of p38alpha-deficient cells. Moreover, mice deficient in p38alpha are prone to cancer development using carcinogen or oncogene-induced cancer models. p38alpha can suppress cell proliferation by antagonizing the JNK/c-Jun pathway, which is an important regulator of proliferation and apoptosis. These findings suggest that therapeutic inhibition of p38 might lead to unwanted proliferation. Therefore, a combined inhibition of p38 and other pathways, such as the JNK pathway, should be considered for targeting cancer inflammation.
authors.affiliation: Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
authors.forename: Latifa
authors.initials: L
authors.lastname: Bakiri
authors.forename: Ewa
authors.initials: E
authors.lastname: Stepniak
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D048308:Mitogen-Activated Protein Kinase 14