Format

Send to

Choose Destination
Cancer Cell. 2017 Jul 10;32(1):115-128.e7. doi: 10.1016/j.ccell.2017.06.001.

Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.

Author information

1
Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
2
Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
3
Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
4
Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
5
Department of Hematology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
6
The Integrative Genomics Core, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
7
Division of Comparative Medicine, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
8
Division of Hematopoietic Stem Cell & Leukemia Research, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
9
Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA; Department of Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
10
Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA; Department of Pathology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
11
Department of Hematology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: zrxyk10@zju.edu.cn.
12
Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA. Electronic address: whuang@coh.org.

Abstract

Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKIIγ levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

KEYWORDS:

CAMKIIγ; T cell lymphoma; c-MYC; c-Myc stabilization; phosphorylation

PMID:
28697340
PMCID:
PMC5552197
DOI:
10.1016/j.ccell.2017.06.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center