主催: 公益社団法人日本薬理学会
会議名: 第97回日本薬理学会年会
回次: 97
開催地: 神戸
開催日: 2023/12/14 - 2023/12/16
We have elucidated that the ubiquitin ligase RNF183 is specifically expressed in the kidney, especially in the collecting ducts, which are constantly exposed to hyperosmotic stress. We also identified NKCC1 as a substrate protein of RNF183 using the proximal biotin labeling method with RNF183 fused with the biotin ligase BirA.
In this study, we examined the role of ubiquitination of NKCC1 by RNF183. This analysis was conducted using HEK293 cells expressing RNF183 by the Tet-on system. Our results suggest that RNF183 ubiquitinates NKCC1, promoting its lysosomal degradation. Additionally, in mIMCD cells, which show induced expression of endogenous Rnf183 under hyperosmotic stress, we generated Rnf183-KO cells and examined whether cell death increased or decreased under this stress. The result indicated that the expression of cleaved caspase-3 was elevated in Rnf183-KO cells.
A recent study reported that the expression of RNF183 is upregulated in the colons of patients with inflammatory bowel disease (IBD). Since the molecular mechanisms underlying the development and pathophysiology of IBD are not fully understood, IBD is designated as an intractable disease. Therefore, we plan to analyze the relationship between RNF183 expression and hyperosmotic stress in colon cells and the effects of increased RNF183 expression.
