Inhibitors of apoptosis proteins (IAPs) block signals that promote apoptosis. Vucic et al. have identified a new IAP from melanoma cells, termed ML-IAP. Mutation of the ML-IAP BIR (baculovirus IAP repeat) motif, which is essential for the anti-apoptosis effect of IAPs, disrupted the ability of ML-IAP to prevent apoptosis induced by chemotherapeutic agents or by activation of death receptors. The authors showed that ML-IAP was expressed in all melanoma cell lines tested but not in normal human melanocytes. These results suggest that overexpression of IAPs can bestow resistance to chemotherapeutic agents on cancer cells. Additionally, it may be beneficial to use rational design for clinical drugs that target IAPs for cancer therapy. For more information on IAPs, read the outstanding Perspective by Richter and Duckett.
Vucic, D., Stennicke, H.R., Pisabarro, M.T., Salvesen, G.S., and Dixit, V.M. (2000) ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr. Biol. 10: 1359-1366. [Online Journal]
Richter, B.,W., M., and Duckett, C. S. (2000) The IAP proteins: caspase inhibitors and beyond. Science's STKE: http://www.stke.org/cgi/content/full/OC_sigtrans;2000/44/pe1. [Full Text]