title: PIAS1 negatively regulates ubiquitination of Msx1 homeoprotein independent of its SUMO ligase activity.
abstract: Posttranslational modifications play key roles in many cellular processes including proliferation and differentiation by modulating the activities of target proteins. PIAS1, a member of PIAS family of protein, mediates the modification of protein by SUMO and thereby regulates the function of its interacting protein partners. Here we report that PIAS1 negatively regulates ubiquitination of Msx1 homeoprotein, a regulator of myogenic differentiation, in a SUMO-independent manner. We demonstrate that ubiquitination and SUMOylation of Msx1 are not mutually exclusive but require the same C-terminal PIAS1 interaction domain. In addition, deletion of C-terminal domain increases the steady-state protein level of Msx1, while mutations of SUMO acceptor sites have no significant effect on the stability of Msx1 proteins. Moreover, we find that forced expression of PIAS1 inhibits ubiquitination and thereby increases the stability of Msx1 protein regardless of its activity as a SUMO ligase. Furthermore, repressor activity of Msx1 in transcription is strengthened in the presence of PIAS1. Taken together, our studies uncover a new function of PIAS1, which is to control the stability of its interacting protein partner in a SUMO independent manner.
authors: Department of Biological Sciences, College of Natural Science, Inha University, Incheon 402-751, Korea.
authors: Young Joon
authors: YJ
authors: Song
authors: Hansol
authors: H
authors: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection; D054875:Ubiquitination / Q000235:genetics*
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; C484084:Msx1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011993:Recombinant Fusion Proteins; D025842:SUMO-1 Protein; D008156:Luciferases