UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response.

ABSTRACT: Despite the pivotal role of MYC in tumorigenesis, the mechanisms by which it promotes cancer aggressiveness remain incompletely understood. Here, we show that MYC transcriptionally upregulates the ubiquitin fusion degradation 1 (UFD1) gene in T-cell acute lymphoblastic leukemia (T-ALL). Allelic loss of ufd1 in zebrafish induces tumor cell apoptosis and impairs MYC-driven T-ALL progression but does not affect general health. As the E2 component of an endoplasmic reticulum (ER)-associated degradation (ERAD) complex, UFD1 facilitates the elimination of misfolded/unfolded proteins from the ER. We found that UFD1 inactivation in human T-ALL cells impairs ERAD, exacerbates ER stress, and induces apoptosis. Moreover, we show that UFD1 inactivation promotes the proapoptotic unfolded protein respon

SUBMITTER: Huiting LN 

PROVIDER: S-EPMC6202254 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature