Cellular inhibitor of apoptosis protein-1 (cIAP-1) is an anti-apoptotic protein that is able to bind to caspases and inhibit their activity. Additionally cIAP-1 contains a RING domain with E3 ubiquitin ligase activity that is able to mediate the regulation of NF-kB signaling through the ubiquitination and degradation of various substrate proteins. Depending on cellular context, the RING domain of cIAP-1 can either promote or inhibit apoptosis. cIAP-1 functions in many cellular processes including inflammation, apoptosis, and the unfolded protein response making it an important player and potential target in various pathological conditions. For example, cIAP-1 levels were found to be a useful prognostic marker for the diagnosis and treatment of bladder cancer (1). Given the increased expression of cIAP-1 in cancer, small molecules targeting cIAP-1 for degradation have shown promise for sensitizing cancer cells to apoptosis (2). Depletion of IAP family proteins not only sensitizes cells to apoptosis but inhibits proliferation and cell survival. Monitoring the expression levels of IAP proteins represents a useful method for characterizing the resistance mechanisms of cancer cells. In a study by Zinonos et al. a panel of antibodies including the cIAP-1 antibody was used to measure levels of apoptosis related proteins in cancer cells resistant to drozitumab (3). Similarly, Tassi et al. used the cIAP-1 antibody in flow cytometry to examine the levels of anti-apoptotic proteins in drug resistant melanoma cells (4). Additionally, this study used western blotting with the cIAP-1 antibody to reveal differences in IAP induction depending on the specific cancer causing mutation present. The authors were able to characterize the role of the IAP protein BIRC6 in melanoma drug resistance. cIAP-1 antibodies have also been used in immunoprecipitation experiments to identify interactions between IAPs and to characterize these heteromeric protein complexes (5). These findings suggest a complex regulatory relationship between the IAPs. Together these studies show the importance of cIAP-1 antibodies in the investigation of cancer cells in designing effective drug treatments and in understanding cancer cell survival mechanisms.
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