Function
IAPs were discovered in baculoviruses and were shown to be involved in suppressing the host cell response to viral infection. [1]
- Baculoviral IAP repeat-containing protein 1 (BIRC1 or NAIP) inhibits the activities of caspase-3,7,9. BIRC1 acts as mediator of neuronal survival in pathological conditions and prevents motor-neuron apoptosis.
- Baculoviral IAP repeat-containing protein 2 (cIAP1) and Baculoviral IAP repeat-containing protein 3 (cIAP2) inhibit apoptosis by interfering with the activation of caspase and by binding to TNFR-associated factors TRAF1 and TRAF2. cIAP1 is a multi-functional protein which acts as an E3 ubiquitin-protein ligase and plays a role in the modulation of the cell cycle. cIAP1 is involved in controlling b-cell survival under ER stress caused by lipotoxicity. Both cIAP1 and cIAP2 regulate NF-kB activation. cIAP2 inhibits apoptosis caused by serum deprivation but not by inducers of free radicals.
- For Baculoviral IAP repeat-containing protein 4 see XIAP in Ubiquitin protein ligase.
- For Baculoviral IAP repeat-containing protein 5 see Survivin.
- Baculoviral IAP repeat-containing protein 6 (BIRC6) inhibits caspase-3,7,9. Has a role in the final stages of cytokinesis, vescilcle targeting to the site of abscission and ubiquitin conjugation.
- Baculoviral IAP repeat-containing protein 7 or melanoma inhibitor of apoptosis (ML-IAP) contains one BIR and one RING domain. ML-IAP has 2 isoforms. Isoform-a protects cells from staurosporine-induced apoptosis and isoform-b protects cells from etoposide-induced apoptpsis.
- Baculoviral IAP repeat-containing protein 8 (BIRC8).
Disease
cIAP1 is a target for intervention against type 2 diabetes. Mutated or deleted BIRC1 were found in individuals with severe muscular atrophy.
Relevance
IAP proteins suppress cell death by inhibiting the activity of caspases. As they are involved in apoptosis regulation, IAPs are of interest in cancer and autoimmune diseases therapy.
Structural highlights
cIAPs domains include 3 BIR (zinc-finger found in apoptosis inhibitors) domains in the N-terminal, a UBA (Ubiquitin-Associated), CARD (Caspase Recruitment) and RING finger (zinc finger which contains Cys3-His-Cys4 motif) domain in the C-terminal.
in human Baculoviral IAP repeat-containing protein 2 BIR3 domain (PDB code 3d9t)[2]
