ABSTRACT
The identification, now more than 20 years ago, of the first iap genes in baculoviruses subsequently led to many important discoveries concerning the regulation of apoptosis and other important biological processes in insects and mammals. Currently there are more than 200 known viral IAP homologs in baculoviruses and other families of invertebrate DNA viruses. This review begins with a personal account of the events leading up to the discovery of the first iap genes, followed by a summary of what is currently known about the different types of viral IAPs and their functions in regulating apoptosis, and possibly other cellular processes.
Subject(s)
Inhibitor of Apoptosis Proteins/history , Inhibitor of Apoptosis Proteins/metabolism , Viral Proteins/history , Viral Proteins/metabolism , Animals , Apoptosis , History, 20th Century , Inhibitor of Apoptosis Proteins/chemistry , Inhibitor of Apoptosis Proteins/genetics , Phylogeny , Viral Proteins/chemistry , Viral Proteins/geneticsSubject(s)
Inflammation/history , Inhibitor of Apoptosis Proteins/history , Signal Transduction/genetics , Tumor Necrosis Factors/history , Animals , History, 20th Century , History, 21st Century , Humans , Inflammation/genetics , Inhibitor of Apoptosis Proteins/metabolism , Mice , NF-kappa B/metabolism , Receptors, Tumor Necrosis Factor/genetics , Receptors, Tumor Necrosis Factor/history , Receptors, Tumor Necrosis Factor/metabolism , Tumor Necrosis Factors/metabolismABSTRACT
BCL-2 was the first antideath gene discovered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.
