Journal
EMBO JOURNAL
Volume 40, Issue 7, Pages -Publisher
WILEY
DOI: 10.15252/embj.2020105846
Keywords
C-degron pathway; CRL2 ubiquitin ligase; N-degron pathway; protein spatial quality control; protein termini
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Funding
- Data Science Statistical Cooperation Center of Academia Sinica [AS-IA-108-L02]
- Taiwan Protein Project
- MOST from the National Science Council of Taiwan [107-2321-B-001-021, 108-2321-B-001-006]
- Academia Sinica
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The study elucidates the function of C-degron pathways in removing mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. It also shows that normal proteins targeted by C-degron pathways experience a shortfall, highlighting proteolysis-based immunity as a constraint for protein evolution/selection. The cooperation between C-degron and N-degron pathways in protein removal is also emphasized.
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino- or carboxyl-termini are eliminated by the N- or C-degron pathways, respectively. We aimed to elucidate the function of C-degron pathways and to unveil how normal proteomes are exempt from C-degron pathway-mediated destruction. Our data reveal that C-degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C-degron and N-degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C-degron pathways, but not of defective proteins, suggesting proteolysis-based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways.
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