RIPK1 binds to vitamin D receptor and decreases vitamin D-induced growth suppression

摘要: Receptor interacting protein kinase 1 (RIPK1) is an enzyme acting downstream of tumor necrosis factor alpha to control cell survival and death. RIPK1 expression has been reported cause drug resistance in cancer cells, but so far, no published studies have investigated the role vitamin D signaling. In present study, we whether plays any roles 1,25-dihydroxyvitamin D3 (1,25D3)-induced growth suppression. our studies, decreased transcriptional activity receptor (VDR) luciferase reporter assays independent its activity, suggesting a negative 1,25D3 action. also formed complex with VDR, deletion analyses mapped binding region C-terminal ligand-binding domain VDR. Subcellular fractionation indicated that increased VDR retention cytoplasm, which may account for inhibition activity. Consistent analyses, 1,25D3-induced suppression was more pronounced RIPK1-null MEFs RIPK1-knockdown ovarian cells than cells. Our defined as repressor, projecting depletion potential strategy increase potency analogs intervention.