title: The p53 oncoprotein is a substrate for tissue transglutaminase kinase activity.
abstract: Increased expression and activity of the ubiquitous enzyme, tissue transglutaminase (TG2), is consistently seen in a variety of models of apoptosis. The p53 oncoprotein is also involved in apoptosis. Here we investigated the interaction of TG2 with p53 and show that the p53 is a substrate for the recently identified serine/threonine kinase activity of TG2. Phosphospecific antibodies indicated that TG2 phosphorylated p53 at Ser(15) and Ser(20), residues that are critically important in the interaction of p53 with Mdm2. The TG2-induced phosphorylation was abrogated by high Ca(2+) concentrations and inhibited by cystamine, a known inhibitor of TG2 cross-linking activity. Furthermore, we demonstrate that TG2-induced phosphorylation of p53 reduces the ability of p53 to interact with Mdm2. Although TG2 cross-linking activity has been clearly implicated in apoptosis, our observations reported here suggest TG2 modification of p53 could be an additional mechanism whereby TG2 could facilitate apoptosis.
authors.affiliation: Department of Physiology, University of Manitoba, Winnipeg, Canada R3E 0W3.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mishra
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murphy
mesh_terms: D002460:Cell Line; D019204:GTP-Binding Proteins; D006801:Humans; D010766:Phosphorylation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013379:Substrate Specificity; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins