钙调蛋白激酶IIγ（CAMKIIγ）对c-Myc蛋白的稳定作用促进T细胞淋巴瘤。
Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.
作者信息
Gu Ying, Zhang Jiawei, Ma Xiaoxiao, Kim Byung-Wook, Wang Hailong, Li Jinfan, Pan Yi, Xu Yang, Ding Lili, Yang Lu, Guo Chao, Wu Xiwei, Wu Jun, Wu Kirk, Gan Xiaoxian, Li Gang, Li Ling, Forman Stephen J, Chan Wing-Chung, Xu Rongzhen, Huang Wendong
机构信息
Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
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.
出版信息
Cancer Cell. 2017 Jul 10;32(1):115-128.e7. doi: 10.1016/j.ccell.2017.06.001.
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, Ca/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.
尽管在某些癌症中，c-Myc蛋白高表达与MYC基因扩增同时出现，但在大多数情况下，蛋白过表达发生在基因未扩增时，如T细胞淋巴瘤（TCL）。在此研究中，钙/钙调蛋白依赖性蛋白激酶IIγ（CAMKIIγ）被证明可通过直接在丝氨酸62（S62）位点磷酸化c-Myc蛋白来使其稳定。此外，CAMKIIγ被证明对肿瘤维持至关重要。用特异性抑制剂抑制CAMKIIγ会使c-Myc不稳定并减轻肿瘤负荷。重要的是，患者TCL标本中CAMKIIγ水平升高与c-Myc及磷酸化S62-c-Myc水平增加相关。总之，CAMKIIγ:c-Myc轴对TCL的发生发展和维持起着关键作用，是TCL的一个潜在治疗靶点。
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