KIX domain determines a selective tumor-promoting role for EP300 and its vulnerability in small cell lung cancer.

ABSTRACT: EP300, a transcription coactivator important in proliferation and differentiation, is frequently mutated in diverse cancer types, including small cell lung cancer (SCLC). While these mutations are thought to result in loss of EP300 function, the impact on tumorigenesis remains largely unknown. Here, we demonstrate that EP300 mutants lacking acetyltransferase domain accelerate tumor development in mouse models of SCLC. However, unexpectedly, complete Ep300 knockout suppresses SCLC development and proliferation. Dissection of EP300 domains identified kinase inducible domain-interacting (KIX) domain, specifically its interaction with transcription factors including MYB, as the determinant of protumorigenic activity. Ala⁶²⁷ in EP300 KIX results in a higher protein-binding aff

SUBMITTER: Kim KB 

PROVIDER: S-EPMC8849394 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature