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PIAS1 Promotes Lymphomagenesis through MYC Upregulation. Cell Rep 2016 06 07;15(10):2266-2278

Date

05/31/2016

Pubmed ID

27239040

Pubmed Central ID

PMC4899214

DOI

10.1016/j.celrep.2016.05.015

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.

Author List

Rabellino A, Melegari M, Tompkins VS, Chen W, Van Ness BG, Teruya-Feldstein J, Conacci-Sorrell M, Janz S, Scaglioni PP

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carcinogenesis
Cell Line
Cell Proliferation
Cell Survival
Gene Expression Regulation, Neoplastic
Half-Life
Humans
Lymphoma, B-Cell
Mice
Phosphorylation
Phosphothreonine
Protein Binding
Protein Inhibitors of Activated STAT
Proteolysis
Proto-Oncogene Proteins c-myc
Sumoylation
Transcription, Genetic
Up-Regulation
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc