PIAS1 Promotes Lymphomagenesis through MYC Upregulation

Andrea Rabellino, Margherita Melegari, Van S. Tompkins, Weina Chen, Brian G. Van Ness, Julie Teruya-Feldstein, Maralice Conacci-Sorrell, Siegfried Janz, Pier Paolo Scaglioni

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2266-2278
Number of pages13
JournalCell Reports
Volume15
Issue number10
DOIs
StatePublished - Jun 7 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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