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The regulation of transcriptional activation by NF-κB p52 homodimer and proto-oncogenic Bcl3
Wang, V. Y.-F.
2024-09-02
Size of Audience100
Type of SpeakerInvited Speaker
AbstractThe binding of transcription factors (TFs) to their specific DNA response elements in the promoters/enhancers of target genes is the key event regulating gene transcription and consequent cellular events. The NF-κB family of TFs plays a critical role in diverse physiological processes. Our study focuses on the transcriptional regulation by one NF-κB family member, p52, and its specific co-factor, B-cell lymphoma 3 (Bcl3). Bcl3 is an oncoprotein, the constitutive nuclear presence of Bcl3 induces chronic inflammation and proliferation. Bcl3 is also extensively phosphorylated, it associates with NF-κB p52 homodimers to regulate transcription. Using the combination of structural and biochemical studies, we have shown 1) Bcl3 plays an essential role in enhancing p52:p52 homodimer population in cells which is an unique mechanism to p52 within NF-κB family. 2) Crystal structures of p52:p52 homodimer in complex with its natural κB DNA target site(s) revealed a widening of the DNA minor groove compared to all previously known structures of NF-κB-DNA complexes; further MD simulations studies provide new insights into allosteric control by closely related κB DNAs on NF-κB-dependent transcriptional specificity. 3) Phospho-modification mediated changes in Bcl3 regulate DNA accommodation by the Bcl3:(p52:p52) complex. Overall, our studies shed lights on the intricate structural changes driven by both DNA and protein conformation and dynamic states in modulating transcriptional activity.
Conference DateSept 02-04, 2024
Conference PlaceMarburg, Germany
Funding ProjectInvestigation of IκB:NF-κB:DNA Ternary Complex ; Mechanistic Study of NFkappaB and Oncoprotein Bcl3 in Transcriptional Regulation ; Investigation of molecular mechanism of Epstein-Barr virus infection and its translational research
Language英語English
Document TypePresentation
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorWang, V. Y.-F.
AffiliationUniversity of Macau
Recommended Citation
GB/T 7714
Wang, V. Y.-F.. The regulation of transcriptional activation by NF-κB p52 homodimer and proto-oncogenic Bcl3, Sept 02-04, 2024.
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