ELP3 stabilizes c-Myc to promote tumorigenesis

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.