Paper Details
- Kentaro Oh-hashi (Graduate School of Natural Science and Technology, Gifu University / Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University / United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University / Center for One Medicine Innovative Translational Research (COMIT), Gifu University / oh-hashi.kentaro.u7@f.gifu-u.ac.jp)
1) Graduate School of Natural Science and Technology, Gifu University , 2) Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 3) United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University , 4) Center for One Medicine Innovative Translational Research (COMIT), Gifu University
EDEM2 plays an important role as the first enzyme that acts during mannose trimming of N-glycosylated proteins in the ERAD machinery. Although EDEM2 expression has been reported to be transcriptionally regulated by the IRE1-sXBP1 pathway, very little is known about how endogenous EDEM2 protein expression is regulated. In this work, three different ER stress inducers were used to treat HEK293 cells. Thapsigargan slightly increased both EDEM2 mRNA and protein levels in the cells. Treatment with MG132 did not increase the level of mature EDEM2 protein, and a truncated form of the protein appeared. In SEL1L-deficient cells, there was a slight increase in EDEM2 protein as well as in TXNDC11, a protein that has been reported to form disulfide bonds with EDEM2. On the other hand, EDEM2 protein level decreased in TXNDC11-deficient cells. DTT treatment decreased EDEM2 and TXNDC11 protein levels in a time-dependent manner. The decrease in EDEM2 protein after DTT treatment was attenuated by treatment of the cells with MG132 and by SEL1L deficiency. These findings demonstrate that endogenous EDEM2 protein is regulated posttranscriptionally and that it is in part an SEL1L-mediated ERAD substrate.
