title: Targeting p38 MAP kinase signaling in cancer through post-translational modifications.
abstract: The p38 MAPK signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli, and has attracted much attention as a promising target for cancer therapy. Accumulating evidence suggests a dual role of p38 signaling in various types of cancers, wherein the p38 pathway can both suppress and promote tumor growth, metastasis and chemoresistance. This dual role of p38 signaling, along with its context dependence and versatility, poses a great challenge for developing efficient anticancer treatment. An increasing number of studies showed that p38 signaling is subject to regulation by a variety of post-translational modifications (PTMs). Recently, large-scale proteomics profilings have identified a large number of PTMs on key components of the p38 pathway. However, the majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we highlight a series of studies that focus on the PTMs in the p38 cascade landscape, and discuss the complexity and implications of these PTMs in p38 MAPK signaling regulation.
authors.affiliation: Laboratory of Molecular and Cellular Cancer Biology, Faculty of Medicine, Bar-Ilan University, Safed, Israel.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zou
authors.affiliation: Laboratory of Molecular and Cellular Cancer Biology, Faculty of Medicine, Bar-Ilan University, Safed, Israel. Electronic address: michael.blank@biu.ac.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Blank
mesh_terms: D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D054875:Ubiquitination; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cancer; Chemotherapy; PTM; Ubiquitination; p38 MAPK signaling pathway