| Residential College | false |
| Status | 已發表Published |
| The regulation of transcriptional activation by NF-κB p52 homodimer and proto-oncogenic Bcl3 | |
Wang, V. Y.-F. 
| |
| 2024-07-22 | |
| Size of Audience | 30 |
| Type of Speaker | Invited Speaker |
| Abstract | The 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 processes. The nuclear factor κB (NF-κB) family of TFs plays a critical role in diverse physiological processes including the immune response, inflammation, cell proliferation and survival. 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, which has been implicated in a wide range of cancers, both hematological and solid tumors. The constitutive nuclear presence of Bcl3 induces chronic inflammation and proliferation by maintaining high levels of cyclin D1 and inflammatory cytokines, controlling both tumor growth and proliferation. Bcl3 is an extensively phosphorylated protein which associates with NF-κB p52 homodimers to regulate transcription. The aberrant activation of Bcl3 and p52 leads to cancers. 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 the 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 Place | Hong Kong Baptist University |
| Funding Project | Investigation 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 |
| Document Type | Presentation |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES |
| Corresponding Author | Wang, V. Y.-F. |
| Affiliation | Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China |
| First Author Affilication | Faculty of Health Sciences |
| Recommended Citation GB/T 7714 | Wang, V. Y.-F.. The regulation of transcriptional activation by NF-κB p52 homodimer and proto-oncogenic Bcl3 |
| Files in This Item: | Download All | |||||
| File Name/Size | Publications | Version | Access | License | ||
| HKBU_2024.jpg（8922KB） | 演讲报告 | 开放获取 | CC BY-NC-SA |  View Download | ||
| File name: | HKBU_2024.jpg |
| Format: | JPEG |
| Resolution: | 4032x3024 |
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