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.

journal_name

Cell Rep

journal_title

Cell reports

authors

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

doi

10.1016/j.celrep.2016.05.015

subject

Has Abstract

pub_date

2016-06-07 00:00:00

pages

2266-2278

issue

10

issn

2211-1247

pii

S2211-1247(16)30583-6

journal_volume

15

pub_type

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