Eukaryotic Transcriptional Activation Mechanism: Protein-Protein Interactions

<p>Various in vivo and in vitro assays have been employed to analyze how activators communicate with the general transcription machinery to stimulate transcription. As a first step, I analyzed the function of distinct kinds of activation domains in yeast and human. The results showed that the proline-rich activation domain of CTF1 can, like acidic activation domains, activate transcription in yeast and human. Based on this, I compared the activation pathways by acidic and proline-rich activation domains in yeast and human. These detailed comparative approaches yielded clues to the fundamental aspects of transcriptional activation mechanism in eukaryotes: activators target TFIID (TBP)-TFIIB promoter complex formation in the preinitiation complex assembly process by inducing (or stabilizing) qualitative or quantitative alterations within TFIID (TBP)-TFIIB-promoter complexes that consequently enhance recruitment of downstream initiation factors. Consistent with this view, various activation domains have been demonstrated to have physical and functional interactions with TBP and/or TFIIB. Given the central role of TBP in transcriptional regulation, I also identified distinct TBP domains (or residues) important for different regulatory interactions including those with acidic activators, TFIIB, Dr1 (NC2), Pol I- and Pol III- specific factors. These mutational analyses have provided an insight into how the interplay of many regulatory factors occurs on the surface of a target factor, TBP, to specify and regulate transcriptional activity. Furthermore, I investigated the essential features of the CTF1 proline-rich activation domain and showed that CTD-like sequences (Ser-Pro motifs) are important for activation, possibly by forming a β-turned omega (Ω) loop structure. Thus, the β-turn structure is likely to be a salient secondary structure in the activation domains in addition to a β-sheet structure which was previously proposed for acidic activation domains.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

1994

Author dc:creator

• Kim, Tae Kook

Contributors dc:contributor

• Robert G. Roeder

• transcriptional activation
• activation domains
• TATA-box binding protein (TBP)
• TFIIB
• proline-rich domain
• beta-turn structure
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/373

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1376