Ufmylation Maintains the Proper Er Homeostasis of Pancreas from Alcoholic Rodents

Abstract

The accumulation of misfolded pancreatic enzymes in the rough ER causes an activation of unfolded protein response (UPR). Ufmylation (Ufm1) is a novel post-translational ubiquitin-like modification system involved in UPR. Ufm1 modifies its target proteins through a biochemical pathway that involves E3 ligase. RCAD is an E3 ligase that forms a complex with DDRGK1. Be- cause of the synthesis, folding/sorting of pancreatic enzymes takes place in the rough ER and Ufm1 is involved in ER homeostasis. The first objective was to study the importance of RCAD and DDRGK1 in both proper sorting and secretion of digestive enzymes. We found that the lack of RCAD or DDRGK1 causes an increase in the expression of pancreatic amylase and trypsin activation. Because Ufmylation is involved in rough ER homeostasis and alcoholism causes changes in the expression of multiple rough ER proteins involved in the UPR, the next objective was to compare the relative expression of RCAD and DDRGK1 in alcohol-treated rats with non-treated rats. We found that both RCAD and DDRGK1 are highly expressed in alcohol-treated pancreas. In conclusion, alcoholism could increase the level of these proteins in the exocrine pancreas to protect it from ER stress and inflammation. Funding Source: Center for Undergraduate Research and Scholarship, Department of Biological Sciences and Scholarly Activity Award