Endoplasmic reticulum (ER)-associated degradation of T cell receptor subunits - Involvement of ER-associated ubiquitin-conjugating enzymes (E2s)

Degradation of proteins from the endoplasmic reticulum is fundamental to qu ality control within the secretory pathway, serves as a way of regulating l evels of crucial proteins, and is utilized by viruses to enhance pathogenes is. In yeast two ubiquitin-conjugating enzymes (E2s), UBC6p and UBC7p are i mplicated in this process. We now report the characterization of murine hom ologs of these E2s. MmUBC6 is an integral membrane protein that is anchored via its hydrophobic C-terminal tail to the endoplasmic reticulum. MmUBC7, which is not an integral membrane protein, shows significant endoplasmic re ticulum colocalization with MmUBC6. Overexpression of catalytically inactiv e MmUBC7 significantly delayed degradation from the endoplasmic reticulum o f two T cell antigen receptor subunits, alpha and CD3-delta, and suggests a role for the ubiquitin conjugating system at the initiation of retrograde movement from the endoplasmic reticulum. These findings also implicate, for the first time, a specific E2 in degradation from the endoplasmic reticulu m in mammalian cells.