Proteasomal control of transcription factors: mechanisms, regulation and dysregulation

Regulation of transcription is of key importance for essentially all aspects of biology. Accordingly, transcription factors (TFs) are often subject to rapid degradation, which in turn allows for strict regulation of gene expression and prevents uncontrolled activation or repression of target genes. This rapid turnover is a result of highly effective ubiquitin-dependent and -independent systems specifically selecting individual TFs for proteasomal degradation. The importance of life-time regulation of TFs is underscored by a broad range of diseases connected with dysfunctional TF degradation. Here, we summarize transcriptional regulation through controlled TF degradation. We focus on human TFs and highlight recent advances in our understanding of how TFs are selected for degradation through various proteasomal degradation pathways, and the implications of aberrant TF degradation.