Rush hour at the promoter: how the ubiquitin-proteasome pathway polices the traffic flow of nuclear receptor-dependent transcription.
Nuclear receptor-dependent transcription requires the functional activities of many proteins in order to achieve proper gene expression. Progress in understanding transcription mechanisms has revealed the unexpected involvement of the ubiquitin-proteasome pathway in the transcriptional process. In some instances, stabilization of the transcription protein augments the functional role or activation state of that protein, but other evidence supports the hypothesis that degradation of that factor may be required in order for transcription to proceed. Perhaps most peculiar is the observation that several yeast models support the uncoupling of ubiquitylation from concomitant proteasome-mediated degradation, with the former responsible for regulating posttranslational modification of histones and controlling differential recruitment of a transcription factor to distinct promoters. Additionally, the ATPases of the 19S proteasome regulatory cap have been shown to function in transcription elongation, independently of their role in proteolysis. This review summarizes and discusses progress thus far in integrating the disparate fields of ubiquitylation and proteasome-mediated protein degradation with gene transcription.