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Publication : PIAS1 Promotes Lymphomagenesis through MYC Upregulation.

First Author  Rabellino A Year  2016
Journal  Cell Rep Volume  15
Issue  10 Pages  2266-2278
PubMed ID  27239040 Mgi Jnum  J:238167
Mgi Id  MGI:5818414 Doi  10.1016/j.celrep.2016.05.015
Citation  Rabellino A, et al. (2016) PIAS1 Promotes Lymphomagenesis through MYC Upregulation. Cell Rep 15(10):2266-78
abstractText  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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