PDF(Pubmed)
Abstract：
Most mature B-cell malignancies originate from the malignant transformation of germinal center (GC) B cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is BCL6, a key regulator of this process. We now demonstrate that BCL6 protein levels were dramatically decreased in Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines and Burkitt\'s lymphoma cell lines. Notably, BCL6 degradation was significantly enhanced in the presence of both EBNA3C and FBXO11. Furthermore, the amino-terminal domain of EBNA3C, which contains residues 50-100, interacts directly with FBXO11. The expression of EBNA3C and FBXO11 resulted in a significant induction of cell proliferation. Furthermore, BCL6 protein expression levels were regulated by EBNA3C via the Skp Cullin Fbox (SCF)FBXO11 complex, which mediated its ubiquitylation, and knockdown of FBXO11 suppressed the transformation of lymphoblastoid cell lines. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction and raise the possibility of developing new targeted therapies against EBV-associated cancers.
OBJECTIVE: The novel revelation in our study involves the suppression of BCL6 expression by the essential Epstein-Barr virus (EBV) antigen EBNA3C, shedding new light on our current comprehension of how EBV contributes to lymphomagenesis by impeding the germinal center reaction. It is crucial to note that while several EBV latent proteins are expressed in infected cells, the collaborative mechanisms among these proteins in regulating B-cell development or inducing B-cell lymphoma require additional investigation. Nonetheless, our findings carry significance for the development of emerging strategies aimed at addressing EBV-associated cancers.
OBJECTIVE: The novel revelation in our study involves the suppression of BCL6 expression by the essential Epstein-Barr virus (EBV) antigen EBNA3C, shedding new light on our current comprehension of how EBV contributes to lymphomagenesis by impeding the germinal center reaction. It is crucial to note that while several EBV latent proteins are expressed in infected cells, the collaborative mechanisms among these proteins in regulating B-cell development or inducing B-cell lymphoma require additional investigation. Nonetheless, our findings carry significance for the development of emerging strategies aimed at addressing EBV-associated cancers.
摘要：
大多数成熟的B细胞恶性肿瘤起源于生发中心（GC）B细胞的恶性转化。GC反应似乎在恶性转化中起作用，其中GC反应的主要参与者是BCL6，该过程的关键调节剂。我们现在证明，在EB病毒（EBV）阳性淋巴母细胞样细胞系和伯基特淋巴瘤细胞系中，BCL6蛋白水平显着降低。值得注意的是,BCL6降解在EBNA3C和FBXO11存在下显著增强。此外，EBNA3C的氨基末端结构域，它含有残基50-100，直接与FBXO11相互作用。EBNA3C和FBXO11的表达导致细胞增殖的显著诱导。此外，BCL6蛋白表达水平受EBNA3C通过SkpCullinFbox(SCF)FBXO11复合物调控,介导了它的泛素化，FBXO11的敲除抑制了类淋巴母细胞细胞系的转化。这些数据为EBNA3C在GC反应过程中B细胞转化中的功能提供了新的见解，并提高了开发针对EBV相关癌症的新靶向疗法的可能性。
目的：我们的研究中的新发现涉及通过必需的EB病毒（EBV）抗原EBNA3C抑制BCL6表达，为我们目前对EBV如何通过阻碍生发中心反应促进淋巴生成的理解提供了新的思路。重要的是要注意，虽然几种EBV潜伏蛋白在感染细胞中表达，这些蛋白质在调节B细胞发育或诱导B细胞淋巴瘤方面的协同机制需要进一步研究.尽管如此，我们的研究结果对于制定旨在解决EBV相关癌症的新兴策略具有重要意义.
目的：我们的研究中的新发现涉及通过必需的EB病毒（EBV）抗原EBNA3C抑制BCL6表达，为我们目前对EBV如何通过阻碍生发中心反应促进淋巴生成的理解提供了新的思路。重要的是要注意，虽然几种EBV潜伏蛋白在感染细胞中表达，这些蛋白质在调节B细胞发育或诱导B细胞淋巴瘤方面的协同机制需要进一步研究.尽管如此，我们的研究结果对于制定旨在解决EBV相关癌症的新兴策略具有重要意义.
