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Investigations into Wnt modulation of p27(KIP1) turnover and the E3 ligase substrate adaptor DDB1 and CUL4 Associated Factor 4

Abstract

Wnt signaling plays a major role in cell proliferation, cell fate, and stem cell maintenance. Its regulatory function is achieved through the induction of numerous downstream Wnt target genes. Relatively little work has focused on the influences of Wnt signaling on the ubiquitin proteasome system. Our work has examined Wnt transcriptional modulation of WD40 genes with potential function as E3 ligase substrate adaptors, and we present evidence that DCAF4 is a Wnt target gene. We have confirmed DCAF4 as a component of the CUL4 RING E3 ligase (CRL4) associated protein consistent with previous research. Our research has uncovered differential CRL4 binding amongst its splicing variants and an N-terminal domain that appears to regulate this interaction. We have also revealed a number of novel DCAF4 associated proteins by MudPit mass spectrometry analysis of DCAF4 with the most interesting being components of the prefoldin and BAT3 complexes.

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