Reciprocal antagonism of PIN1-APC/C^CDH1 governs mitotic protein stability and cell cycle entry.

ABSTRACT: Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/C^CDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/C^CDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/C^CDH1 mediated

SUBMITTER: Ke S 

PROVIDER: S-EPMC11018817 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature