Proteomic Assessment Shows That Many Endoplasmic Reticulum (ER)-resident Proteins Are Targeted by Nϵ-Lysine Acetylation in the Lumen of the Organelle and Predicts Broad Biological Impact*
In addition to the nucleus, cytosol, and mitochondrial lumen, Nϵ-lysine acetylation also occurs in the lumen of the endoplasmic reticulum (ER). However, the impact of such an event on ER functions is still unknown. Here, we analyzed the “ER acetyl-lysine proteome” by nano-LC-MS/MS and discovered that a large number of ER-resident and -transiting proteins undergo Nϵ-lysine acetylation in the lumen of the organelle. The list of ER-resident proteins includes chaperones and enzymes involved with post-translational modification and folding. Grouping of all acetylated proteins into major functional categories suggests that the ER-based acetylation machinery regulates very diverse biological events. As such, it is predicted to play a fundamental role in human physiology as well as human pathology.
Background: The functional impact of the Nϵ-lysine acetylation in the lumen of the ER is unknown.
Results: Analysis of the ER acetyl-lysine proteome revealed that many resident and transiting proteins are acetylated in the ER lumen.
Conclusion: The ER-based acetylation machinery regulates very diverse biological events.
Significance: The ER-based acetylation machinery is predicted to play a fundamental role in human physiology and pathology.
