ELP3 stabilizes c-Myc to promote tumorigenesis  

作　　者：Wentao Zhao Cong Ouyang Chen Huang Jiaojiao Zhang Qiao Xiao Fengqiong Zhang Huihui Wang Furong Lin Jinyang Wang Zhanxiang Wang Bin Jiang Qinxi Li 

机构地区：[1]State Key Laboratory of Cellular Stress Biology,School of Life Sciences,Faculty of Medicine and Life Sciences,Xiamen University,Xiamen 361102,China [2]Department of Neurosurgery and Department of Neuroscience,Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment,Xiamen Key Laboratory of Brain Center,the First Affiliated Hospital of Xiamen University,School of Medicine,Xiamen University,Xiamen 361003,China

出　　处：《Journal of Molecular Cell Biology》2023年第9期40-52,共13页分子细胞生物学报（英文版）

基　　金：supported by grants from China Postdoctoral Science Foundation(2022M712672);the National Natural Science Foundation of China(U21A20373 and 32070749).

摘　　要：ELP3,the catalytic subunit of the Elongator complex,is an acetyltransferase and associated with tumor progression.However,the detail of ELP3 oncogenic function remains largely unclear.Here,we found that ELP3 stabilizes c-Myc to promote tumorigenesis in an acetyltransferase-independent manner.Mechanistically,ELP3 competes with the E3-ligase FBXW7βfor c-Myc binding,resulting in the inhibition of FBXW7β-mediated ubiquitination and proteasomal degradation of c-Myc.ELP3 knockdown diminishes glycolysis and glutaminolysis and dramatically retards cell proliferation and xenograft growth by downregulating c-Myc,and such effects are rescued by the reconstitution of c-Myc expression.Moreover,ELP3 and c-Myc were found overexpressed with a positive correlation in colorectal cancer and hepatocellular carcinoma.Taken together,we elucidate a new function of ELP3 in promoting tumorigenesis by stabilizing c-Myc,suggesting that inhibition of ELP3 is a potential strategy for treating c-Myc-driven carcinomas.

关 键 词：ELP3 C-MYC FBXW7 Elongator 

分 类 号：Q78[生物学—分子生物学]