Degradation of selenoprotein S and selenoprotein K through PPARγ-mediated ubiquitination is required for adipocyte differentiation.

Adipocyte differentiation is known to be related with endoplasmic reticulum (ER) stress. We have reported that selenoprotein S (SelS) and selenoprotein K (SelK) have a function in the regulation of ER stress and ER-associated degradation. However, the association between adipocyte differentiation and the ER-resident selenoproteins, SelS and SelK, is unclear. In this study, we found that the levels of SelS and SelK were decreased during adipocyte differentiation and were inversely related to the levels of peroxisome proliferator-activated receptor γ (PPARγ), a central regulator of adipogenesis. It has been recently reported that PPARγ has E3 ubiquitin ligase activity. Here, we report that PPARγ directly interacts with both SelS and SelK via its ligand-binding domain to induce ubiquitination and degradation of the selenoproteins. Lysine residues at the 150th position of SelS and the 47th and 48th positions of SelK were the target sites for ubiquitination by PPARγ. We also found that adipocyte differentiation was inhibited when either SelS or SelK was not degraded by PPARγ. Thus, these data indicate that PPARγ-mediated ubiquitination and degradation of SelS and SelK is required for adipocyte differentiation.