Identification of the E3 Ubiquitin Ligase of Transcription Factor Taf2 for Future Therapeutic Intervention
Publisher
University of Tennessee at Chattanooga
Place of Publication
Chattanooga (Tenn.)
Abstract
Abstract: Taf2, a core subunit of the TFIID complex, is essential for RNA polymerase II–mediated transcription. Taf2 is highly conserved from Saccharomyces cerevisiae to humans and is overexpressed in hepatocellular carcinoma (HCC) and high-grade serous ovarian cancer (HGSC); however, the mechanism underlying its accumulation remains unknown. Protein abundance is tightly regulated by the ubiquitin–proteasome system (UPS), in which E3 ubiquitin ligases confer substrate specificity. Preliminary evidence indicates that Taf2 is regulated by the UPS, yet the responsible E3 ligase has not been identified.
We hypothesize that Taf2 protein levels are controlled by a specific E3 ubiquitin ligase and that disruption of this regulatory pathway leads to Taf2 accumulation, contributing to cancer-associated transcriptional dysregulation. Western blot analysis of Taf2 (~161 kDa) in wild-type (BY4741) yeast and ten E3 ligase deletion strains (Δrad7, Δasi1, Δmdm30, Δbre1, Δrad18, Δsan1, Δnot4, Δasi3, Δrad16, and Δrad5) did not identify a candidate ligase, suggesting additional E3s may be involved. Further screening of additional E3 ligase mutants is underway.
Identifying the E3 ligase responsible for Taf2 degradation will uncover a novel post-translational mechanism regulating transcription. These findings may explain Taf2 overexpression in cancer and reveal a potential therapeutic target. Future studies will validate Taf2–E3 ligase interactions, map Taf2 ubiquitination sites, examine effects on global transcription, and extend the analysis to mammalian cancer models.
Document Type
abstracts (summaries)
Language
English
Rights
http://rightsstatements.org/vocab/InC/1.0/
License
http://creativecommons.org/licenses/by/4.0/
Recommended Citation
Turner, Allison; Minkara, Maya; Osborn, Morgan; Kaplanoğlu, Selin; and Ferdoush, Jannatul, "Identification of the E3 Ubiquitin Ligase of Transcription Factor Taf2 for Future Therapeutic Intervention". ReSEARCH Dialogues Conference proceedings. https://scholar.utc.edu/research-dialogues/2026/presentations/10.
Identification of the E3 Ubiquitin Ligase of Transcription Factor Taf2 for Future Therapeutic Intervention
Abstract: Taf2, a core subunit of the TFIID complex, is essential for RNA polymerase II–mediated transcription. Taf2 is highly conserved from Saccharomyces cerevisiae to humans and is overexpressed in hepatocellular carcinoma (HCC) and high-grade serous ovarian cancer (HGSC); however, the mechanism underlying its accumulation remains unknown. Protein abundance is tightly regulated by the ubiquitin–proteasome system (UPS), in which E3 ubiquitin ligases confer substrate specificity. Preliminary evidence indicates that Taf2 is regulated by the UPS, yet the responsible E3 ligase has not been identified.
We hypothesize that Taf2 protein levels are controlled by a specific E3 ubiquitin ligase and that disruption of this regulatory pathway leads to Taf2 accumulation, contributing to cancer-associated transcriptional dysregulation. Western blot analysis of Taf2 (~161 kDa) in wild-type (BY4741) yeast and ten E3 ligase deletion strains (Δrad7, Δasi1, Δmdm30, Δbre1, Δrad18, Δsan1, Δnot4, Δasi3, Δrad16, and Δrad5) did not identify a candidate ligase, suggesting additional E3s may be involved. Further screening of additional E3 ligase mutants is underway.
Identifying the E3 ligase responsible for Taf2 degradation will uncover a novel post-translational mechanism regulating transcription. These findings may explain Taf2 overexpression in cancer and reveal a potential therapeutic target. Future studies will validate Taf2–E3 ligase interactions, map Taf2 ubiquitination sites, examine effects on global transcription, and extend the analysis to mammalian cancer models.