biostudies-literatureWang XNCI NIH HHSNational Institutes of HealthSusan G Komen FoundationNIGMS NIH HHSJimmy V-Foundatione00609-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC5472828biostudies-literatureUnknown37(13)The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4^VprBP), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is ligase independent. This implies a nonproteolytic activation mechanism that isMolecular and cellular biologyVprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1.PMC5472828R01GM120309T32 GM007040NAP30 CA016086CCR14298820R01 GM120309Emanuele MJZhou CKernan JLBird KArceci AWang XBowers AChoudhury RMills CABae-Jump VfalseVprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1.The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4^VprBP), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is ligase independent. This implies a nonproteolytic activation mechanism that is2017-01-01T00:00:00Z2017 Jul2026-05-05T15:45:41.338Z2019-03-27T02:47:47ZS-EPMC54728282841663510.1128/MCB.00609-1610.1128/mcb.00609-16