Selenoprotein K: a study into its role in ER stress modulation and ERAD

Abstract

Selenoproteins constitute a distinct protein family characterized by the incorporation of the 21st amino acid, selenocysteine (Sec or U). While some are well-characterized, there is limited in-depth knowledge on the structure and cellular roles of membrane-bound selenoprotein – one of which is selenoprotein K (selenok). Selenok is an intrinsically disordered endoplasmic reticulum (ER) membrane protein that has been reported to be upregulated during ER stress, a condition characterized by the accumulation of misfolded proteins in the ER. It has also been reported to play a role in protein quality control by associating with key players in the endoplasmic reticulum-associated protein degradation (ERAD) pathway, which retro-translocate misfolded proteins from the ER to the cytosol for proteasomal degradation. However, the specific roles of selenok in these cellular processes and pathways are not known. By employing cellular fractionation to investigate selenok’s localization under different conditions, enzymatic deglycosylation to identify selenok’s glycosylation, and purification of selenok and its ERAD partners, this work provides a foundation for investigating the physiological role of selenok in the ERAD pathway.