PIAS1 promotes lymphomagenesis through MYC upregulation Journal Article

Authors: Rabellino, A.; Melegari, M.; Tompkins, V. S.; Chen, W.; Van Ness, B. G.; Teruya-Feldstein, J.; Conacci-Sorrell, M.; Janz, S.; Scaglioni, P. P.
Article 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. © 2016 The Author(s).
Journal Title: Cell Reports
Volume: 15
Issue: 10
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2016-06-07
Start Page: 2266
End Page: 2278
Language: English
DOI: 10.1016/j.celrep.2016.05.015
PROVIDER: scopus
PMCID: PMC4899214
PUBMED: 27239040
Notes: Article -- Export Date: 1 July 2016 -- Source: Scopus
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MSK Authors
  1. Julie T Feldstein
    290 Feldstein