Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma
Ying Gu, Jiawei Zhang, Xiaoxiao Ma, Byung-wook Kim, Hailong Wang, Jinfan Li, Yi Pan, Yang Xu, Lili Ding, Lu Yang, Chao Guo, Xiwei Wu, Jun Wu, Kirk Wu, Xiaoxian Gan, Gang Li, Ling Li, Stephen J. Forman, Wing-Chung Chan, Rongzhen Xu, Wendong Huang
Index: 10.1016/j.ccell.2017.06.001
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Abstract
Although high c-Myc protein expression is observed alongsideMYCamplification 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.