Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates transcription of target genes. In this study, we identified CDK11(p58) as a novel protein involved ill the regulation of VDR. CDK11(p58), a member of the large family of p34cdc2-related kinases, is associated with cell cycle progression, tumorigenesis, and apoptotic signaling. Our study demonstrated that CDK11(p58) interacted with VDR and repressed VDR-dependent transcriptional activation. Furthermore, overexpression of CDK11(p58), decreased the stability of VDR through promoting its ubiquitin-proteasome-mediated degradation. Taken together, these results suggest that CDK11(p58) is involved in the negative regulation of VDR. (C) 2009 Elsevier Inc. All rights reserved.