Stabilization of the c-Myc Protein by CAMKII gamma Promotes T Cell Lymphoma

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

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Stabilization of the c-Myc Protein by CAMKII gamma Promotes T Cell Lymphoma

机译：Camkii Gamma促进C-Myc蛋白的稳定促进T细胞淋巴瘤

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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 gamma (CAMKII gamma) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKII gamma was shown to be essential for tumor maintenance. Inhibition of CAMKII gamma with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKII gamma levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKII gamma:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

机译：尽管在某些癌症中，在一些癌症中观察到高C-myc蛋白表达，但在大多数情况下，在没有基因扩增的情况下发生蛋白质过度表达，例如，发生蛋白质过度表达。 G.，T细胞淋巴瘤（TCL）。这里，显示Ca2 + /钙调蛋白依赖性蛋白激酶IIγ（Camkii Gamma）通过直接在丝氨酸62（S62）中直接磷酸化稳定C-Myc蛋白。此外，Camkiiγ显示对肿瘤维护至关重要。抑制特异性抑制剂破坏性C-MYC的CAMKIIγ和肿瘤负荷降低。重要的是，患者TCL样品中的高Camkiiγ水平与C-Myc和PS62-C-Myc水平增加相关。 Camkii Gamma：C-Myc轴重视TCL的开发和维持，代表TCL的潜在治疗靶标。

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《Cancer Cell》 |2017年第1期|共21页
作者
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;
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作者单位

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Pathol Hangzhou 310009 Zhejiang Peoples R China;

Tianjin Med Univ Canc Inst &

Hosp Natl Clin Res Ctr Canc Key Lab Canc Prevent &

Therapy Dept;

Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Hematol Hangzhou 310009 Zhejiang Peoples R China;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Integrat Genom Core Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Integrat Genom Core Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Integrat Genom Core Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Div Comparat Med Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Div Hematopoiet Stem Cell &

Leukemia Res Duarte CA;

City Hope Natl Med Ctr Beckman Res Inst Irell &

Manella Grad Sch Biol Sci Duarte CA 91010 USA;

City Hope Natl Med Ctr Beckman Res Inst Irell &

Manella Grad Sch Biol Sci Duarte CA 91010 USA;

Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Hematol Hangzhou 310009 Zhejiang Peoples R China;

City Hope Natl Med Ctr Beckman Res Inst Mol &

Cellular Biol Canc Program Duarte CA 91010 USA;

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正文语种 eng
中图分类肿瘤学;
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2. Stabilization of the c-Myc Protein by CAMKII gamma Promotes T Cell Lymphoma [J] . Gu Ying, Zhang Jiawei, Ma Xiaoxiao, Cancer Cell . 2017,第1期

机译：Camkii Gamma促进C-Myc蛋白的稳定促进T细胞淋巴瘤
3. Matrine suppresses cell growth of diffuse large B-cell lymphoma via inhibiting CaMKIIγ/c-Myc/CDK6 signaling pathway [J] . Jianyou Gu, Xiao Wang, Ling Zhang, BMC Complementary and Alternative Medicine . 2021,第1期

机译：苦参碱通过抑制CAMKIIγ/ C-MYC / CDK6信号通路抑制弥漫性大B细胞淋巴瘤的细胞生长
4. c-Myc Proteolysis by the Ubiquitin-Proteasome Pathway: Stabilization of c-Myc in Burkitt's Lymphoma Cells [J] . Mark A. Gregory, Stephen R. Hann Molecular and Cellular Biology . 2000,第7期

机译：通过泛素-蛋白酶体途径的c-Myc蛋白水解：伯基特淋巴瘤细胞中c-Myc的稳定化。
5. Imaging and Mapping Individual Target Proteins on Clinical Lymphoma Cells by AFM [C] . Mi Li, Lianqing Liu, Ning Xi, IEEE International Conference on Nano/Molecular Medicine and Engineering . 2015

机译：通过AFM成像和映射临床淋巴瘤细胞上的个体靶蛋白
6. Sindbis virus usurps the cellular HUR protein to stabilize its transcripts and promote infections of mammalian and mosquito cells. [D] . Sokoloski, Kevin J. 2010

机译：Sindbis病毒篡夺了细胞中的HUR蛋白，以稳定其转录本并促进哺乳动物和蚊子细胞的感染。
7. Stabilization of the c-Myc protein by CAMKIIγ promotes T cell lymphoma [O] . Ying Gu, Jiawei Zhang, Xiaoxiao Ma, -1

机译：CAMKIIγ稳定c-Myc蛋白可促进T细胞淋巴瘤
8. c-Myc Proteolysis by the Ubiquitin-Proteasome Pathway: Stabilization of c-Myc in Burkitt's Lymphoma Cells [O] . Gregory, Mark A., Hann, Stephen R. 2000

机译：通过泛素-蛋白酶体途径的c-Myc蛋白水解：伯基特淋巴瘤细胞中c-Myc的稳定化。

Stabilization of the c-Myc Protein by CAMKII gamma Promotes T Cell Lymphoma

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