Many misfolded endoplasmic reticulum (ER) proteins are eliminated by ERAD, a process in which substrates are polyubiquitylated and moved into the cytosol for proteasomal degradation. We have identified in S. cerevisiae distinct ubiquitin-ligase complexes that define different ERAD pathways. Proteins with misfolded ER-luminal domains use the ERAD-L pathway, in which the Hrd1p/Hrd3p ligase forms a near stoichiometric membrane core complex by binding to Der1p via the linker protein Usa1p. This core complex associates through Hrd3p with Yos9p, a substrate recognition protein in the ER lumen. Substrates with misfolded intramembrane domains define a pathway (ERAD-M) that differs from ERAD-L by being independent of Usa1p and Der1p. Membrane proteins with misfolded cytosolic domains use the ERAD-C pathway and are directly targeted to the Doa10p ubiquitin ligase. All three pathways converge at the Cdc48p ATPase complex. These results lead to a unifying concept for ERAD that may also apply to mammalian cells.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.cell.2006.05.043 | DOI Listing |
Hum Mol Genet
January 2025
Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.
Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.
BMC Genomics
January 2025
Key Laboratory of Ecological Protection and Restoration of Typical Plateau Wetlands, Bijie, Guizhou Province, 551700, China.
Background: Temperature is a key determinant of ectotherms distribution and growth. During the Eriocheir sinensis breeding process, it was observed that crabs in high latitudes and altitude areas with low temperatures undergo diapause, they would overwinter and continue to grow into three-year-old individuals, whose final body size is significantly larger than the normal two-year-old crabs. The hepatopancreas is responsible for maintaining the nutritional balance and energy required for the crab survival.
View Article and Find Full Text PDFSci Total Environ
January 2025
Department of Arctic and Marine Biology, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
Increased industrial offshore activities in northern waters raise the question of impact of polycyclic aromatic hydrocarbons (PAHs) on key Arctic marine species. One of these is the ecologically important polar cod (Boreogadus saida), which is the primary food source for Arctic marine mammals and seabirds. In the present work, we have conducted the first comprehensive proteomics study with this species by exploring the effects of dietary PAH exposure on the hepatic proteome, using benzo[a]pyrene (BaP) as a PAH model-compound.
View Article and Find Full Text PDFEur J Med Chem
December 2024
SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address:
Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.
View Article and Find Full Text PDFNat Chem
January 2025
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
Amyloid fibrils are highly stable misfolded protein assemblies that play an important role in several neurodegenerative and systemic diseases. Although structural information of the amyloid state is now abundant, mechanistic details about the misfolding process remain elusive. Inspired by the Φ-value analysis of protein folding, we combined experiments and molecular simulations to resolve amino-acid contacts and determine the structure of the transition-state ensemble-the rate-limiting step-for fibril elongation of PI3K-SH3 amyloid fibrils.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!