PIAS1 Promotes Lymphomagenesis through MYC Upregulation

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. [Display omitted] •PIAS1 is a MYC SUMO E3 ligase•PIAS1 increases MYC phosphorylation thus increasing its transcriptional activity•PIAS1 is required for the viability of MYC-dependent B cell lymphoma cells•PIAS1 is highly expressed in MYC-driven B cell lymphomas Rabellino et al. find that the SUMO E3 ligase PIAS1 promotes activation of the proto-oncogene MYC in a SUMOylation-dependent manner. PIAS1 is co-expressed with MYC in B cell lymphomas and is required for the viability of MYC-driven B cell lymphoma cells.