CK1δ stimulates ubiquitination-dependent proteasomal degradation of ATF4 to promote chemoresistance in gastric Cancer.

ABSTRACT: Chemoresistance remains a major obstacle to successful cancer therapy, especially for advanced cancers. It used to be recognised as a stable outcome resulting from genetic changes. However, recent studies showed that chemoresistance can also be unstable and reversible with the involvement of non-genetic alterations. In the present study, we found that activating transcription factor 4 (ATF4) is downregulated in chemoresistant gastric cancer cells. The over-expression of ATF4 reversed chemoresistance by activating CHOP transcription to enhance drug-induced apoptosis, and vice versa. Moreover, casein kinase 1 delta (CK1δ) was identified as the kinase responsible for ATF4-S219 phosphorylation, which triggered βTrCP-mediated ATF4 polyubiquitination to promote its proteasomal degradation subseq

SUBMITTER: Feng L 

PROVIDER: S-EPMC8516343 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature