| Status | 已發表Published |
| Structural Study of Transcription Factor NF-kB subunit p52 and Oncoprotein Bcl3 | |
Wang, V. Y.-F. 
| |
| 2016-11-25 | |
| Source Publication | The 4th Structural Biology Forum in South China Abstract Book
 |
| Abstract | NF-kB constitutes a family of dimeric transcription factors which regulate a broad spectrum of physiological processes such as inflammation, immune response, cell survival, and cell proliferation1. An important function of NF-kB is to prevent programmed cell death or apoptosis, through the induction of anti-apoptotic factors. NF-kB also activates genes that are responsible for cell proliferation. In combination, these two activities can contribute to uncontrolled cell growth. Indeed, uncontrolled NF-kB activity has been reported in several cancer cells. One of the NF-kB family members, p52, is linked to the increased occurance of cellular transformation, due to its role in both cell cycle control and the regulation of tumor suppressor protein p53. p52 primarily functions as a heterodimer with other family members. Structurally, p52 does not have a classical transcription activation domain, but instead, has a short glycine rich region (GRR) which caps its C-terminus. The function of GRR in transcription, if any, is unknown. The p52 homodimer requires a coactivator for transcriptional activation. Several studies have shown that Bcl3 is the specific coactivator for p522. Bcl3 was originally identified as a putative proto-oncogene which is upregulated transcriptionally in some cases of human B-cell chronic lymphocytic leukemia. Bcl3 is a member of the inhibitor of NF-kB (IkB) family and is present predominantly in the nucleus. Mice deficient in both p52 and Bcl3, but not either one alone, led to a profound breakdown in central tolerance resulting in rapid and fatal multiorgan inflammation3. Thus, demonstrating that p52 and Bcl3 functions together to regulates genes at the transcriptional level which are important for immune tolerance. Our recent study has shown that the p52:Bcl3 complex participates in the coordination of biological programs, such as the control of inflammation and proliferation4. The complex controls inflammation by activating a class of anti-inflammatory cytokines such as IL-10, by binding to their G/C-centric kB sites; and at the same time, the complex may repress pro-inflammatory cytokines such as IL-23, IL-6 and IL-8, and other inflammatory factors such as NOS2, COX2, and prostaglandin E synthase by binding to their A/T-centric kB sites. Our observation is consistent with the report that p52 and Bcl3 jointly tamper inflammation of effector genes that would otherwise undergo uncontrolled expression as seen in nfkb2-/-bcl3-/- double knockout mice. Through the highly selective regulation of G/C-centric kB sites within the promoters of Skp2 and CyclinD1, the p52:Bcl3 complex controls cell proliferation. The transcriptional activation of CyclinD1 from a specific kB site is well-documented. Because these two promoters contains only G/C-centric kB sites, the absolute requirement for p52 and Bcl3 in the activation, and in turn, cell cycle regulation, can now be properly explained. Here we proposed the study of the detailed mechanism of p52:Bcl3 complex formation and DNA recognition at the atomic level by determine the three-dimensional structure of the complex, allowing us better understanding of their cellular functions. |
| Keyword | NF-kB p52 Bcl3 |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 57354 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES |
| Corresponding Author | Wang, V. Y.-F. |
| Recommended Citation GB/T 7714 | Wang, V. Y.-F.. Structural Study of Transcription Factor NF-kB subunit p52 and Oncoprotein Bcl3[C], 2016. |
| APA | Wang, V. Y.-F..(2016). Structural Study of Transcription Factor NF-kB subunit p52 and Oncoprotein Bcl3. The 4th Structural Biology Forum in South China Abstract Book. |
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