Reactome | XIAP binds CASP3

XIAP binds CASP3

Stable Identifier

R-HSA-9627104

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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X‑linked inhibitor of apoptosis protein (XIAP) suppresses cell death by inhibiting the catalytic activity of caspases (Deveraux QL et al. 1997; Paulsen M et al. 2008). XIAP consists of three bacculoviral inhibitory repeat (BIR) domains and a C‑terminal ring finger. Biochemical and structural analyses revealed that the linker connecting BIR1 to BIR2 inhibits executioner caspase‑3 and ‑7 by positioning itself at the active site (Sun C et al. 1999; Riedl SJ et al. 2001; Huang Y et al. 2001; Chai J et al. 2001). Formation of a complex between caspase‑3 or caspase‑7 and the XIAP BIR2‑linker region appears to be driven by interactions between XIAP's Leu141 and Val146 and a hydrophobic site present on both caspases. This hydrophobic site is not found in caspase‑8 or caspase‑9, perhaps explaining the binding specificity of XIAP (Riedl SJ et al. 2001). BIR2 domain of XIAP may also contribute to inhibition of executioner caspases by interacting with additional sites on the enzymes (Scott FL et al. 2005; Abhari BA & Davoodi J 2008).

Literature References

PubMed ID	Title	Journal	Year
15650747	XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs Scott, FL, Denault, JB, Riedl, SJ, Shin, H, Renatus, M, Salvesen, GS	EMBO J.	2005
11257231	Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain Huang, Y, Park, YC, Rich, RL, Segal, D, Myszka, DG, Wu, H	Cell	2001
11230124	Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes Bratton, SB, Walker, G, Srinivasula, SM, Sun, XM, Butterworth, M, Alnemri, ES, Cohen, GM	EMBO J.	2001