Regulation of transcription is critical for the maintenance of normal cellular homeostasis. Failure to regulate transcription can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of transcription is by making extensive use of the proteolytic activities of the Ubiquitin Proteasome System (UPS). The evolutionary conserved UPS is involved in targeted degradation of transcription factors (TFs) and thus regulates transcription. Dysregulation of UPS-mediated degradation of TFs could lead to overexpression of TFs in cells, thereby could lead to oncogenesis. Importantly, TFs, Paf1 and Taf2 are overexpressed in many cancers 1-5, however, the basis for overexpression of TFs, Paf1 and Taf2 in cancer cells are unclear. In UPS, E3 ligases are essential in understanding molecular mechanisms as it possess the substrate specificity. Although Not4 is the E3 ligase in UPS regulation of Paf1 6,7, the mechanism of Not4-mediated UPS regulation of Paf1 in regulating transcription is not clear. Moreover, it is yet unknown the E3 ligase involved in UPS regulation of Taf2. Therefore, we proposed two aims: Aim 1: Investigation of Paf1 ubiquitination and proteasomal degradation in regulation of transcription. Aim 2: Identification of the E3 ligase involved in UPS regulation of Taf2
Ferdoush et al. (Tue,) studied this question.