Journal article
PIAS1 Promotes Lymphomagenesis through MYC Upregulation
Cell reports (Cambridge), Vol.15(10), pp.2266-2278
06/07/2016
DOI: 10.1016/j.celrep.2016.05.015
PMCID: PMC4899214
PMID: 27239040
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.
Details
- Title: Subtitle
- PIAS1 Promotes Lymphomagenesis through MYC Upregulation
- Creators
- Andrea Rabellino - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAMargherita Melegari - Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAVan S Tompkins - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAWeina Chen - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USABrian G Van Ness - Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USAJulie Teruya-Feldstein - Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAMaralice Conacci-Sorrell - Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USASiegfried Janz - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAPier Paolo Scaglioni - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: pier.scaglioni@utsouthwestern.edu
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.15(10), pp.2266-2278
- DOI
- 10.1016/j.celrep.2016.05.015
- PMID
- 27239040
- PMCID
- PMC4899214
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- R01 CA151354 / NCI NIH HHS P30 CA142543 / NCI NIH HHS P50 CA070907 / NCI NIH HHS R01 CA137195 / NCI NIH HHS P30 CA008748 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 06/07/2016
- Academic Unit
- Pathology
- Record Identifier
- 9984083274802771
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