PIAS1 Promotes Lymphomagenesis through MYC Upregulation

Andrea Rabellino, Margherita Melegari, Van S. Tompkins, Weina Chen, Brian G. Van Ness, Julie Teruya-Feldstein, Maralice Conacci-Sorrell, Siegfried Janz, Pier Paolo Scaglioni

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Aug 28 2015

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B-Cell Lymphoma
Sumoylation
Up-Regulation
Cells
Ubiquitin-Protein Ligases
Proto-Oncogenes
Post Translational Protein Processing
Threonine
Phosphorylation
Serine
Neoplasms
Transcription Factors
Cell Line
Chemical activation
Defects

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rabellino, A., Melegari, M., Tompkins, V. S., Chen, W., Van Ness, B. G., Teruya-Feldstein, J., ... Scaglioni, P. P. (Accepted/In press). PIAS1 Promotes Lymphomagenesis through MYC Upregulation. Cell Reports. https://doi.org/10.1016/j.celrep.2016.05.015

PIAS1 Promotes Lymphomagenesis through MYC Upregulation. / Rabellino, Andrea; Melegari, Margherita; Tompkins, Van S.; Chen, Weina; Van Ness, Brian G.; Teruya-Feldstein, Julie; Conacci-Sorrell, Maralice; Janz, Siegfried; Scaglioni, Pier Paolo.

In: Cell Reports, 28.08.2015.

Research output: Contribution to journalArticle

Rabellino A, Melegari M, Tompkins VS, Chen W, Van Ness BG, Teruya-Feldstein J et al. PIAS1 Promotes Lymphomagenesis through MYC Upregulation. Cell Reports. 2015 Aug 28. https://doi.org/10.1016/j.celrep.2016.05.015
Rabellino, Andrea ; Melegari, Margherita ; Tompkins, Van S. ; Chen, Weina ; Van Ness, Brian G. ; Teruya-Feldstein, Julie ; Conacci-Sorrell, Maralice ; Janz, Siegfried ; Scaglioni, Pier Paolo. / PIAS1 Promotes Lymphomagenesis through MYC Upregulation. In: Cell Reports. 2015.
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