Search

The article explores national and state-based use and cost of infliximab (IFX) and adalimubab (ADA) for treatment of luminal and fistulizing Crohn's disease and acute severe ulcerative colitis under the Pharmaceutical Benefits Scheme (PBAC) between January 2007 and July 2014. Topics discussed include the exponential increase in IFX and ADA usage while still remaining within PBAC projections and marked geographical heterogeneity in anti-tumor necrosis factor usage.

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. SYNOPSIS: Proteins with degradation signals (degron) at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. Proteome‐wide analyses suggest functions of human C‐degrons signals in protein quality surveillance, as well as interplay with N‐degron‐dependent mechanisms. The Global Protein Stability (GPS) random peptide platform enables context‐independent characterization of degron features.The activity of C‐degrons is tuned by their surrounding sequences.Gly/C‐degron shortage is limited to functional eukaryotic proteomes accessible to C‐degron pathways.C‐degron pathways clear products of proteases and mislocalized cellular proteins.Mitochondrial localization of MIC19 is dually safeguarded by the N‐ and C‐degron pathways.Coronaviral diGly‐ending proteins evade C‐degron pathway‐mediated degradation. [ABSTRACT FROM AUTHOR]