Decoupling the role of ubiquitination for the dislocation versus degradation of major histocompatibility complex (MHC) class i proteins during endoplasmic reticulum-associated degradation (ERAD)

Background: Whether ubiquitination of endoplasmic reticulum-associated degradation substrate is required for dislocation remains unresolved. Results: Mutant major histocompatibility complex I (MHCI) heavy chains lacking tails or lysine residues are dislocated in a deubiquitinating enzyme-dependent manner. Conclusion: Ubiquitination of MHCI heavy chains is not required for dislocation as it is required for degradation. Significance: Our data support a model that dislocation and degradation require two mechanistically distinct ubiquitination events.