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Oncogene. 2013 Nov 7;32(45):5283-91. doi: 10.1038/onc.2012.543. Epub 2012 Nov 26.

STK38 is a critical upstream regulator of MYC's oncogenic activity in human B-cell lymphoma.

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1
Joint Centers for Systems Biology, Columbia University, New York, NY, USA.

Abstract

The MYC protooncogene is associated with the pathogenesis of most human neoplasia. Conversely, its experimental inactivation elicits oncogene addiction. Besides constituting a formidable therapeutic target, MYC also has an essential function in normal physiology, thus creating the need for context-specific targeting strategies. The analysis of post-translational MYC activity modulation yields novel targets for MYC inactivation. Specifically, following regulatory network analysis in human B-cells, we identify a novel role of the STK38 kinase as a regulator of MYC activity and a candidate target for abrogating tumorigenesis in MYC-addicted lymphoma. We found that STK38 regulates MYC protein stability and turnover in a kinase activity-dependent manner. STK38 kinase inactivation abrogates apoptosis following B-cell receptor activation, whereas its silencing significantly decreases MYC levels and increases apoptosis. Moreover, STK38 knockdown suppresses growth of MYC-addicted tumors in vivo, thus providing a novel viable target for treating these malignancies.

PMID:
23178486
PMCID:
PMC3715597
DOI:
10.1038/onc.2012.543
[Indexed for MEDLINE]
Free PMC Article

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