title: PIAS1 Promotes Lymphomagenesis through MYC Upregulation.
abstract: The MYC proto-oncogene is a transcription factor implicated in a broad range of cancers. MYC is regulated by several post-translational modifications including SUMOylation, but the functional impact of this post-translational modification is still unclear. Here, we report that the SUMO E3 ligase PIAS1 SUMOylates MYC. We demonstrate that PIAS1 promotes, in a SUMOylation-dependent manner, MYC phosphorylation at serine 62 and dephosphorylation at threonine 58. These events reduce the MYC turnover, leading to increased transcriptional activity. Furthermore, we find that MYC is SUMOylated in primary B cell lymphomas and that PIAS1 is required for the viability of MYC-dependent B cell lymphoma cells as well as several cancer cell lines of epithelial origin. Finally, Pias1-null mice display endothelial defects reminiscent of Myc-null mice. Taken together, these results indicate that PIAS1 is a positive regulator of MYC.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rabellino
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Margherita
authors.initials: M
authors.lastname: Melegari
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Van S
authors.initials: VS
authors.lastname: Tompkins
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Weina
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Van Ness
authors.affiliation: Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Maralice
authors.initials: M
authors.lastname: Conacci-Sorrell
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: pier.scaglioni@utsouthwestern.edu.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Scaglioni
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D059748:Proteolysis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D010769:Phosphothreonine