A Systematic Protein Turnover Map for Decoding Protein Degradation.
Cell Rep
; 33(6): 108378, 2020 11 10.
Article
em En
| MEDLINE
| ID: mdl-33176155
ABSTRACT
Protein degradation is mediated by an expansive and complex network of protein modification and degradation enzymes. Matching degradation enzymes with their targets and determining globally which proteins are degraded by the proteasome or lysosome/vacuole have been a major challenge. Furthermore, an integrated view of protein degradation for cellular pathways has been lacking. Here, we present an analytical platform that combines systematic gene deletions with quantitative measures of protein turnover to deconvolve protein degradation pathways for Saccharomyces cerevisiae. The resulting turnover map (T-MAP) reveals target candidates of nearly all E2 and E3 ubiquitin ligases and identifies the primary degradation routes for most proteins. We further mined this T-MAP to identify new substrates of ER-associated degradation (ERAD) involved in sterol biosynthesis and to uncover regulatory nodes for sphingolipid biosynthesis. The T-MAP approach should be broadly applicable to the study of other cellular processes, including mammalian systems.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
/
Proteínas de Saccharomyces cerevisiae
/
Proteólise
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article