The Epstein-Barr virus latent membrane protein 1 (LMP1) enhances TNF alpha-induced apoptosis of intestine 407 epithelial cells: the role of LMP1 C-terminal activation regions 1 and 2.
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) can protect some kinds of lymphocytes from apoptotic cell death. In contrast, the present study showed that the expression of LMP1 induced high susceptibility to tumor necrosis factor alpha (TNFalpha)-induced apoptosis in intestine 407 epithelial cells, without affecting expression of TNF receptors I and II. LMP1-deletion mutants lacking either C-terminal activation region (CTAR)-1 or CTAR-2 had ability to enhance TNFalpha-induced apoptosis, whereas the deletion of both activation regions completely abolished the induction of high susceptibility to TNFalpha. Phosphorylation of the NFkB-inhibitory molecule IkB-alpha, another biological activity of TNFalpha, was not enhanced by LMP1-expression. LMP1 upregulated antiapoptotic gene A20 expression, suggesting that A20 can not block TNFalpha-induced apoptosis in this cell system. Apoptosis triggered by TNFalpha in LMP1-expressing intestine 407 cells was blocked by inhibitors of caspases-8 and -3. It is therefore concluded that in intestine 407 epithelial cells, LMP1 enhances primarily signal cascade responsible for TNFalpha-induced apoptosis, which occurs at a level upstream of acting site of caspases-8 and -3 and that CTAR-1 and CTAR-2 are involved in enhancement of TNFalpha-induced apoptosis.
Kawanishi
M
M
Department of Microbiology, Kyoto University, Kyoto, 606-8315, Japan. kawanisi@mb.med.kyoto-u.ac.jp
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology* / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000502:physiology*; D014779:Virus Replication
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins