E3 ligase adaptor FBXO7 contributes to ubiquitination and proteasomal degradation of SIRT7 and promotes cell death in response to hydrogen peroxide.

ABSTRACT: Parkinson's disease (PD) is a degenerative disorder of the central nervous system that affects 1% of the population over the age of 60. Although aging is one of the main risk factors for PD, the pathogenic mechanism of this disease remains unclear. Mutations in the F-box-only protein 7 (FBXO7) gene have been previously found to cause early onset autosomal recessive familial PD. FBXO7 is an adaptor protein in the SKP1-Cullin-1-F-box (SCF) E3 ligase complex that facilitates the ubiquitination of substrates. Sirtuin 7 (SIRT7) is an NAD⁺-dependent histone deacetylase that regulates aging and stress responses. In this study, we identified FBXO7 as a novel E3 ligase for SIRT7 that negatively regulates intracellular SIRT7 levels through SCF-dependent Lys-48-linked polyubiquitination an

SUBMITTER: Lee SH 

PROVIDER: S-EPMC9971319 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature