ERAD

Introduction Endoplasmic Reticulum Associated Protein Degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by the proteasome.

The process can be divided in three steps:
 * Recognition of misfolded proteins in the endoplasmic reticulum
 * Retro-translocation into the cytosol
 * Ubiquitin-dependent degradation by the proteasome

Forms of ERAD

ERAD can be subdivided into three distinct processes depending on the substrate protein.
 * ERAD-L: Membrane proteins with misfolded ER luminal domain and soluble ER proteins.
 * ERAD-C: Membrane proteins with a misfolded cytoplasmatic domain.
 * ERAD-M: Membrane spanning proteins with a defect in the transmembrane region.

ERAD ubiquitination machinery

The ER membrane anchored RING finger containing ubiquitin ligases Hrd1 and Doa10 are the major mediators of substrate ubiquitination during ERAD. The tail anchored membrane protein Ubc6 as well as Ubc1 and the Cue1 dependent membrane bound Ubc7 are the ubiquitin conjugating enzymes involved in ERAD.

Questions

The big questions for ERAD are:
 * How are misfolded proteins recognized?
 * What is the channel for the retrotranslocation of luminal ER proteins?