Inhibitor of apoptosis
Encyclopedia
The Inhibitors of Apoptosis (IAP) are a family of functionally- and structurally-related proteins, which serve as endogenous inhibitors of programmed cell death (apoptosis
). A common feature of all IAPs is the presence of a BIR (Baculovirus IAP Repeat, a ~70 amino acid domain) in one to three copies. The human IAP family consists 8 members, and IAP homologs have been identified in numerous organisms.
The first members of the IAPs identified were from the baculovirus
IAPs, Cp-IAP and Op-IAP, which bind to and inhibit caspases as a mechanism that contributes to its efficient infection and replication cycle in the host. Later, five more human IAPs were discovered which included XIAP
, c-IAPl
, C-IAP2
, NAIP
, and survivin
.
The best characterized IAP is XIAP
, which binds caspase-9
, caspase-3 and caspase 7
, thereby inhibiting their activation and preventing apoptosis
. Also cIAP1 and cIAP2 have been shown to bind caspases, although how the IAPs inhibit apoptosis mechanistically at the molecular level is not completely understood.
Activity of XIAP is blocked by binding to DIABLO
(Smac) and HTRA2
(Omi) proteins released from mitochondria after pro-apoptic stimuli.
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
). A common feature of all IAPs is the presence of a BIR (Baculovirus IAP Repeat, a ~70 amino acid domain) in one to three copies. The human IAP family consists 8 members, and IAP homologs have been identified in numerous organisms.
The first members of the IAPs identified were from the baculovirus
Baculovirus
The baculoviruses are a family of large rod-shaped viruses that can be divided to two genera: nucleopolyhedroviruses and granuloviruses . While GVs contain only one nucleocapsid per envelope, NPVs contain either single or multiple nucleocapsids per envelope. The enveloped virions are further...
IAPs, Cp-IAP and Op-IAP, which bind to and inhibit caspases as a mechanism that contributes to its efficient infection and replication cycle in the host. Later, five more human IAPs were discovered which included XIAP
XIAP
X-linked inhibitor of apoptosis protein also known as inhibitor of apoptosis protein 3 and baculoviral IAP repeat-containing protein 4 is a protein that in humans is encoded by the XIAP gene....
, c-IAPl
BIRC2
Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.-Interactions:...
, C-IAP2
Baculoviral IAP repeat-containing protein 3
Baculoviral IAP repeat-containing protein 3 is a protein that in humans is encoded by the BIRC3 gene.-Interactions:...
, NAIP
NAIP
Baculoviral IAP repeat-containing protein 1 is a protein that in humans is encoded by the NAIP gene.-External links:...
, and survivin
Survivin
Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene....
.
The best characterized IAP is XIAP
XIAP
X-linked inhibitor of apoptosis protein also known as inhibitor of apoptosis protein 3 and baculoviral IAP repeat-containing protein 4 is a protein that in humans is encoded by the XIAP gene....
, which binds caspase-9
Caspase-9
Caspase-9 is an initiator caspase, encoded by the CASP9 gene.CASP9 orthologs have been identified in all mammals for which complete genome data are available. Unique orthologs are also present in lizards, lissamphibians, and teleosts....
, caspase-3 and caspase 7
Caspase 7
Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene.CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available...
, thereby inhibiting their activation and preventing apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Also cIAP1 and cIAP2 have been shown to bind caspases, although how the IAPs inhibit apoptosis mechanistically at the molecular level is not completely understood.
Activity of XIAP is blocked by binding to DIABLO
Diablo homolog
Diablo homolog, mitochondrial is a protein that in humans is encoded by the DIABLO gene . DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC.- Function :...
(Smac) and HTRA2
HtrA serine peptidase 2
Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene.-Interactions:HtrA serine peptidase 2 has been shown to interact with MAPK14, XIAP and BIRC2.-External Links:...
(Omi) proteins released from mitochondria after pro-apoptic stimuli.
See also
- Inhibitor of apoptosis domainInhibitor of apoptosis domainThe inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation...
- XIAPXIAPX-linked inhibitor of apoptosis protein also known as inhibitor of apoptosis protein 3 and baculoviral IAP repeat-containing protein 4 is a protein that in humans is encoded by the XIAP gene....
- cIAP1BIRC2Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.-Interactions:...
- cIAP2
- survivinSurvivinSurvivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene....
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: I32.002