Antagonists of IAP proteins as cancer therapeutics.
Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking apoptosis, modulating signal transduction, and affecting cellular proliferation. Through their interactions with inducers and effectors of apoptosis IAP proteins can effectively suppress apoptosis triggered by diverse stimuli including death receptor signaling, irradiation, chemotherapeutic agents, or growth factor withdrawal. Evasion of apoptosis, in part due to the action of IAP proteins, enhances resistance of cancer cells to treatment with chemotherapeutic agents and contributes to tumor progression. Additionally, IAP genes are known to be subject to amplification, mutation, and chromosomal translocation in human malignancies and autoimmune diseases. In this review we will discuss the role of IAP proteins in cancer and the development of antagonists targeting IAP proteins for cancer treatment.
Dynek
Jasmin N
JN
Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080, USA.
Vucic
Domagoj
D
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B