CPYΔ1 is a poor substrate for ERAD because it lacks a vital sugar.

A major pathway for misfolded proteins is the ER-associated degradation (ERAD) pathway. On page 73, Spear and Ng show that misfolding is not enough to target a protein to ERAD. Rather, particular sugar residues act as signals.

The team used a shortened CPY protein as a model unfolded protein. CPYΔ1 lacked the terminal 154 amino acids of the protein. Surprisingly, it was retained in the ER, rather than being targeted for ERAD. Although CPY contains four N-glycosylation sites, the team found that if they disrupted the last site—the one missing in CPYΔ1—the protein was retained in the ER.To further test whether a single glycan could act as a signal for degradation, the team created two novel mutations in the ERAD substrate proteinase A*. When they mutated the first of two N-glycosylation...

The Rockefeller University Press
2005
The Rockefeller University Press
2005
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