TY - JOUR
T1 - PIAS1 Promotes Lymphomagenesis through MYC Upregulation
AU - Rabellino, Andrea
AU - Melegari, Margherita
AU - Tompkins, Van S.
AU - Chen, Weina
AU - Van Ness, Brian G.
AU - Teruya-Feldstein, Julie
AU - Conacci-Sorrell, Maralice
AU - Janz, Siegfried
AU - Scaglioni, Pier Paolo
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/6/7
Y1 - 2016/6/7
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2016.05.015
DO - 10.1016/j.celrep.2016.05.015
M3 - Article
C2 - 27239040
AN - SCOPUS:84969800844
SN - 2211-1247
VL - 15
SP - 2266
EP - 2278
JO - Cell Reports
JF - Cell Reports
IS - 10
ER -