The N-terminal methionine of cellular proteins as a degradation signal.
Cell
; 156(1-2): 158-69, 2014 Jan 16.
Article
em En
| MEDLINE
| ID: mdl-24361105
ABSTRACT
The Arg/N-end rule pathway targets for degradation proteins that bear specific unacetylated N-terminal residues while the Ac/N-end rule pathway targets proteins through their N(α)-terminally acetylated (Nt-acetylated) residues. Here, we show that Ubr1, the ubiquitin ligase of the Arg/N-end rule pathway, recognizes unacetylated N-terminal methionine if it is followed by a hydrophobic residue. This capability of Ubr1 expands the range of substrates that can be targeted for degradation by the Arg/N-end rule pathway because virtually all nascent cellular proteins bear N-terminal methionine. We identified Msn4, Sry1, Arl3, and Pre5 as examples of normal or misfolded proteins that can be destroyed through the recognition of their unacetylated N-terminal methionine. Inasmuch as proteins bearing the Nt-acetylated N-terminal methionine residue are substrates of the Ac/N-end rule pathway, the resulting complementarity of the Arg/N-end rule and Ac/N-end rule pathways enables the elimination of protein substrates regardless of acetylation state of N-terminal methionine in these substrates.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinais Direcionadores de Proteínas
/
Proteólise
/
Metionina
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article