IAP family proteins—suppressors of apoptosis

  1. Quinn L. Deveraux and
  2. John C. Reed
  1. The Burnham Institute, Program on Apoptosis & Cell Death Research, La Jolla, California 92037 USA

This extract was created in the absence of an abstract.

Apoptosis is a physiological cell suicide program that is critical for the development and maintenance of healthy tissues. Dysregulation of cell death pathways occur in cancer, autoimmune and immunodeficiency diseases, reperfusion injury after ischemic episodes, and in neurodegenerative disorders. Thus, proteins involved in apoptosis regulation are of intense biological interest and many are attractive therapeutic targets.

This review discusses the Inhibitor of Apoptosis (IAP) family of proteins. First discovered in baculoviruses, IAPs were shown to be involved in suppressing the host cell death response to viral infection. Interestingly, ectopic expression of some baculoviral IAPs blocks apoptosis in mammalian cells, suggesting conservation of the cell death program among diverse species and commonalities in the mechanism used by the IAPs to inhibit apoptosis. Although the mechanism used by the IAPs to suppress cell death remains debated, several studies have provided insights into the biochemical functions of these intriguing proteins. Moreover, a variety of reports have suggested an important role for the IAPs in some human diseases.

Structure of IAP family proteins

IAP family proteins are characterized by a novel domain of ∼70 amino acids termed the baculoviral IAP repeat (BIR), the name of which derives from the original discovery of these apoptosis suppressors in the genomes of baculoviruses by Lois Miller and her colleagues (Crook et al. 1993; Birnbaum et al. 1994). Up to three tandem copies of the BIR domain can occur within the known IAP family proteins of viruses and animal species (Fig. ). The conserved presence and spacing of cysteine and histidine residues observed within BIR domains (Cx2Cx6Wx3Dx5Hx6C) suggests that this structure represents a novel zinc-binding fold, but formal proof of this has yet to be obtained.

Structures of BIR domain-containing proteins. The topologies of the known BIR-containing proteins are represented from various …

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