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- Title
Characterization of an anti-apoptotic glycoprotein encoded by Kaposi's sarcoma-associated herpesvirus which resembles a spliced variant of human survivin.
- Authors
Hsei-Wei Wang; Sharp, Tyson V.; Koumi, Andrew; Koentges, Georgy; Boshoff, Chris
- Abstract
We have investigated the expression and function of a novel protein encoded by open reading frame (ORF) K7 of Kaposi's sarcoma-associated herpesvirus (KSHV). Computational analyses revealed that K7 is structurally related to survivin-δEx3, a splice variant of human survivin that protects cells from apoptosis by an undefined mechanism. Both K7 and survivin-δEx3 contain a mitochondrial-targeting sequence, an N-terminal region of a BIR (baculovirus lAP repeat) domain and a putative BH2 (Bcl-2 homology)-like domain. These suggested that K7 is a new viral anti- apoptotic protein and survivin-δEx3 is its likely cellular homologue. We show that K7 is a glycoprotein, which can inhibit apoptosis and anchor to intra- cellular membranes where Bcl-2 resides. K7 does not associate with Bax, but does bind to Bcl-2 via its putative BH2 domain. In addition, K7 binds to active caspase-3 via its BIR domain and thus inhibits the activity of caspase-3. The BH2 domain of K7 is crucial for the inhibition of caspase-3 activity and is therefore essential for its anti-apoptotic function. Furthermore, K7 bridges Bcl-2 and activated caspase-3 into a protein complex. K7 therefore appears to be an adaptor protein and part of an anti-apoptotic complex that presents effector caspases to Bcl-2, enabling Bcl-2 to inhibit caspase activity. These data also suggest that survivin-δEx3 might function by a similar mechanism to that of K7. We denote K7 as vIAP (viral inhibitor- of-apoptosis protein).
- Subjects
KAPOSI'S sarcoma; PROTEINS; HERPESVIRUSES; DNA viruses; GLYCOPROTEINS; GLYCOCONJUGATES
- Publication
EMBO Journal, 2002, Vol 21, Issue 11, p2602
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/21.11.2602