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

被引：39

作者：

Bisikirska, B. C. ^{[1
]}

Adam, S. J. ^{[2
,3
]}

Alvarez, M. J. ^{[1
]}

Rajbhandari, P. ^{[1
]}

Cox, R. ^{[1
,4
]}

Lefebvre, C. ^{[1
]}

Wang, K. ^{[5
,6
]}

Rieckhof, G. E. ^{[1
]}

Felsher, D. W. ^{[2
,3
]}

Califano, A. ^{[1
,5
,7
]}

机构：

[1] Columbia Univ, Joint Ctr Syst Biol, New York, NY USA

[2] Stanford Univ, Div Oncol, Dept Med, Stanford, CA 94305 USA

[3] Stanford Univ, Div Oncol, Dept Pathol, Stanford, CA 94305 USA

[4] Riverdale Country Sch, Bronx, NY USA

[5] Columbia Univ, Dept Biomed Informat, New York, NY USA

[6] Pfizer Inc, San Diego, CA USA

[7] Columbia Univ, Dept Pathol & Genet & Dev, New York, NY USA

来源：

ONCOGENE | 2013年 / 32卷 / 45期

关键词：

STK38; MYC post-translational modifications; protein turnover; transcriptional activity; protein-protein interaction; NDR PROTEIN-KINASE; C-MYC; TRANSCRIPTION FACTOR; TUMOR-REGRESSION; ACTIVATION; COMPLEX; BINDING; DNA; PHOSPHORYLATION; IDENTIFICATION;

D O I：

10.1038/onc.2012.543

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5283 / 5291

页数：9

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