Nuclear export of adenovirus E4orf6 protein is necessary for its ability to antagonize apoptotic activity of BH3-only proteins

Speaker : 鄭達恩                      Place : Room 601

Commentator : 楊倍昌 老師           Time : 15:00~16:00, December 3, 2003

Abstract

 During virus infection, the host cells initiate many defense mechanisms including apoptosis but viruses have their ways to escape. Adenovirus has been defined as an oncogenic virus and the viral gene products, like E1A and E1B, have been defined as oncoproteins. And E4orf6, a 34kD protein coded from the E4 gene is able to facilitate viral mRNA transportation from nucleus to cytoplasm and to enhance cell transformation. Recent studies indicate that E4orf6 involves in p53 degradation and inhibits host cell apoptosis (1). In this paper, the authors showed that E4orf6 prevents cell apoptosis via inhibiting BH3-only proteins. BH3-only proteins including BNIP3 and Bik and etc. are members of Bcl-2-family, are pro-apoptotic proteins that inhibit the anti-apoptotic ability of Bcl-2 (2). The authors also showed that the inhibitory effect of E4orf6 onBH3-only proteins were not mediated by p53-related gene, but by binding to the transmembrane domain of BH3-only proteins directly which is important for localization of the protein on the mitochondria membrane. The authors demonstrated that the nuclear export sequence is necessary for translocating BNIP3 and Bik from mitochondria to cytoplasm (3). All together, it suggests that E4orf6 is exported from the nucleus to cytoplasm and lead, to suppressing the apoptotic activity by binding with BH3-only proteins.

References

1.       Querido, E. et al.(2001). Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex. Genes Dev 15, 3104-17.

2.       Cory, S., and Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2, 647-56.

3.       Aoyagi, M. et al. (2003). Nuclear export of adenovirus E4orf6 protein is necessary for its ability to antagonize apoptotic activity of BH3-only proteins. Oncogene 22, 6919-27.