Research
Regulation of apoptosis by the baculovirus Op-IAP protein
One of the first iap genes discovered was the Op-iap gene from
the baculovirus Orgyia pseudotsugata
nucleopolyhedrovirus (OpMNPV). Expression of the Op-IAP protein protects both insect and mammalian
cells from apoptosis induced by a variety of stimuli. Op-IAP, like most other IAP proteins, contains two
BIR (Baculovirus IAP Repeat) domains at its amino terminus and a RING finger motif at its carboxy terminus.
We have found that the second BIR motif of Op-IAP binds to the amino terminus of the pro-apoptotic
Drosophila protein Hid. However, expression of the second BIR can protect only weakly against Hid-induced
death, indicating that the RING motif of Op-IAP is also important for its anti-apoptotic function. We have
found that the RING motif of Op-IAP has E3 ubiquitin protein ligase activity and is able to direct the
ubiquitination of itself as well as the Hid protein. Thus inactivation of Hid by ubiquitination may be important
in the anti-apoptotic activity of Op-IAP. Finally, many IAP proteins are able to directly inhibit caspases, and
although direct caspase inhibition has not been demonstrated for Op-IAP, we are examining the ability of
Op-IAP to inhibit Drosophila caspases.
We have also used RNA interference (RNAi) to silence the Op-iap gene during OpMNPV infection and
shown that Op-IAP is required to inhibit apoptosis during viral infection.
Wright, C.W. and R.J. Clem. 2002. Sequence requirements for Hid binding and apoptosis regulation in the baculovirus inhibitor of apoptosis Op-IAP: Hid binds Op-IAP in a manner similar to Smac binding of XIAP. J. Biol. Chem. 277:2454-2462.
Means,
J.C., Muro, I., and R.J. Clem.
Silencing
of the baculovirus Op-iap gene by RNA interference reveals its
Green,
M.C., Miller, K., and R.J. Clem. Auto-ubiquitination and ubiquitination of
Hid by the RING domain of
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