The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6

Sun, Kunfeng1; Bose, Dipayan1; Singh, Rajnish Kumar1; Pei, Yonggang2; Robertson, Erle S.1,3

2024-06-01

10.1128/jvi.00548-24

JOURNAL OF VIROLOGY   影响因子和分区

0022-538X

1098-5514

["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.IMPORTANCE 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.","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."]

Epstein-Barr virus EBNA3C FBXO11 E3 ligase ubiquitin

SCI

英语

其他

HHS | NIH | National Cancer Institute (NCI)["R01-CA268998","R01-CA244074"]

Virology

Virology

WOS:001245304000002

AMER SOC MICROBIOLOGY

MICROBIOLOGY

Web of Science

1.Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Tumor Virol Program, Perelman Sch Med, Philadelphia, PA 19104 USA
2.Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Shenzhen, Guangdong, Peoples R China
3.Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

Sun, Kunfeng,Bose, Dipayan,Singh, Rajnish Kumar,et al. The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6[J]. JOURNAL OF VIROLOGY,2024.

Sun, Kunfeng,Bose, Dipayan,Singh, Rajnish Kumar,Pei, Yonggang,&Robertson, Erle S..(2024).The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6.JOURNAL OF VIROLOGY.

Sun, Kunfeng,et al."The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6".JOURNAL OF VIROLOGY (2024).