HRD gene dependence of endoplasmic reticulum-associated degradation.

In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation.

Ubiquitination is used to target both normal proteins for specific regulated degradation and misfolded proteins for purposes of quality control destruction. Ubiquitin ligases, or E3 proteins, promote ubiquitination by effecting the specific transfer of ubiquitin from the correct ubiquitin-conjugating enzyme, or E2 protein, to the target substrate. Substrate specificity is usually determined by ...

Yos9p assists in the degradation of certain nonglycosylated proteins from the endoplasmic reticulum

The HRD ubiquitin ligase recognizes and ubiquitylates proteins of the endoplasmic reticulum that display structural defects. Here, we apply quantitative proteomics to characterize the substrate spectrum of the HRD complex. Among the identified substrates is Erg3p, a glycoprotein involved in sterol synthesis. We characterize Erg3p and demonstrate that the elimination of Erg3p requires Htm1p and ...

Native CYP2C11: heterologous expression in Saccharomyces cerevisiae reveals a role for vacuolar proteases rather than the proteasome system in the degradation of this endoplasmic reticulum protein.

Cytochromes P450 (P450s) are hemoprotein enzymes committed to the metabolism of chemically diverse endo- and xenobiotics. They are anchored to the endoplasmic reticulum (ER) membrane with the bulk of their catalytic domain exposed to the cytosol, and thus they constitute excellent examples of integral monotopic ER proteins. Physiologically they are known to turn over asynchronously, but the det...

Have you HRD? Understanding ERAD Is DOAble!

Numerous factors are involved in the eradication of misfolded proteins, yet how these factors achieve substrate specificity remains unclear. In this issue of Cell, Denic et al. (2006) and Carvalho et al. (2006) report that two distinct protein complexes at the endoplasmic reticulum membrane are responsible for the recognition and degradation of specific subsets of protein substrates.

Dependence of Endoplasmic Reticulum Associated Degradation (ERAD) on the Peptide Binding Domain and Concentration of BiP