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1	CtBPs and IRF3 at the Intersection of Transcriptional Regulation by Macromolecular Complexes Jecrois, Anne M. 13 May 2021 (has links) Transcriptional deregulation has emerged as one of the leading causes in various human diseases. More than fifty percent of cancers arise due to frequent mutations in genes regulating transcription. Higher-order assembly via protein-protein interactions is one common mechanism of transcriptional regulation. Despite their critical role in regulating gene transcription and therapeutic relevance, detailed mechanistic understanding of these assemblies remains scarce. The primary focus of this thesis is to uncover important structural principles underlying the assembly and stability of multi-domain protein assemblies by characterizing components of the IFNβ enhanceosome and the CtBP-mediated repression complex. Using a combination of biochemical and structural analyses, I showed that the transcriptional activator C-terminal binding protein 2 (CtBP2) is a tetramer by solving the 3.6Å cryoEM structure of CtBP2. I highlighted the types of interactions that stabilize the homo-tetramer and showed the relevance of the tetramer in CtBP2 transcriptional activity. Second, I used an integrative approach to investigate the structural features leading to activation of interferon regulator factor 3 (IRF3) and its interaction with DNA. Although this work mostly focused on components of the CtBP2-mediated complex and IFNβ enhanceosome, the principles described here can be applied to other complexes. Therefore, these studies provide an overall understanding on how other macromolecular complexes regulate gene transcription. Furthermore, our structural-based analyses will provide a basis for designing drugs that can regulate gene transcription in cancer and immunological disorders. transcription factors transcription co-activators transcriptional regulation macromolecular complexes CtBPs IRF3 CtBP-mediated repression complex interferon-beta enhanceosome CryoEM homo-tetrameric complexes cancer infectious diseases
2	NOVEL THYROID HORMONE TARGET GENES IN THE LIVER, AND THEIR ROLES IN THYROID HORMONE SIGNALING AND PHYSIOLOGY TALASILA, PHANI KUMAR 26 September 2012 (has links) No description available. Biomedical Research "Thyroid hormone T3 liver energy metabolism lipid metabolism SGK1 ANGPTL4 PI3 kinase GSK650394 transcription angiopoietins oligomerization cleavage LPL LDL VLDL HDL serum triglycerides PGC1a co-activators LPL assay DGGR"

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CtBPs and IRF3 at the Intersection of Transcriptional Regulation by Macromolecular Complexes

NOVEL THYROID HORMONE TARGET GENES IN THE LIVER, AND THEIR ROLES IN THYROID HORMONE SIGNALING AND PHYSIOLOGY