N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity
Résumé
Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal strong genetic dependency between major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both ligase complex UBR4-KCMF1 NatC recognize bearing an unacetylated methionine followed by hydrophobic residue. KO-induced protein degradation phenotypes reversed UBR knockdown, demonstrating central cellular role of this interplay. We loss Drosophila is associated with male sterility, reduced longevity, age-dependent motility due to developmental muscle defects. Remarkably, muscle-specific overexpression UbcE2M, one targeted for KO-mediated degradation, suppresses defects deletion. In conclusion, NatC-mediated acetylation acts as protective mechanism against which relevant increased longevity motility.
Origine | Fichiers éditeurs autorisés sur une archive ouverte |
---|