Open AccessPIAS1 Promotes Lymphomagenesis through MYC Upregulation
Author(s) -
Andrea Rabellino,
Margherita Melegari,
Van S. Tompkins,
Weina Chen,
Brian G. Van Ness,
Julie TeruyaFeldstein,
Maralice ConacciSorrell,
Siegfried Janz,
Pier Paolo Scaglioni
Publication year - 2016
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2016.05.015
Subject(s) - sumo protein , ubiquitin ligase , cancer research , downregulation and upregulation , phosphorylation , null cell , regulator , transcription factor , biology , cell growth , serine , microbiology and biotechnology , chemistry , ubiquitin , cell culture , gene , genetics
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.
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