Reactome | SMAC (DIABLO) binds XIAP

SMAC (DIABLO) binds XIAP

Stable Identifier

R-HSA-9627350

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Programmed Cell Death (Homo sapiens)

- Apoptosis (Homo sapiens)
  - Intrinsic Pathway for Apoptosis (Homo sapiens)
    - Apoptotic factor-mediated response (Homo sapiens)
      - SMAC, XIAP-regulated apoptotic response (Homo sapiens)
        
        SMAC (DIABLO) binds to IAPs (Homo sapiens)
        
        SMAC (DIABLO) binds XIAP (Homo sapiens)

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Second mitochondria derived activator of caspase/direct inhibitor of apoptosis binding protein with low pI (SMAC, also known as DIABLO) is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis (Du C et al. 2000). Mitochondrial import and cleavage of its signal peptide are required for SMAC to gain its apoptotic activity (Du C et al. 2000). In vitro studies revealed that dimerization was required for its function, while monomerization of cytosolic mature SMAC attenuated interaction with XIAP (Chai J et al. 2000; Burke SP & Smith JB 2010). Moreover, SMAC dimer showed high stability in vitro as measured by high hydrostatic pressure, low and high temperatures, and chemical denaturation (Goncalves RB et al. 2008). Binding of SMAC (DIABLO) to the BIR3 region of X linked inhibitor of apoptosis protein (XIAP) competitively inhibits binding of XIAP to caspase 9, while binding to the BIR2 region sterically hinders the interaction of XIAP with CASP3 and CASP7 (Srinivasula SM et al. 2001; Abhari BA & Davoodi J 2008).

Literature References

PubMed ID	Title	Journal	Year
11140638	Structural basis of IAP recognition by Smac/DIABLO Chai, J, Suber, TL, Wang, X, Shi, Y, Wu, JW, Du, C, Wu, G	Nature	2000
11257231	Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain Huang, Y, Wu, H, Rich, RL, Park, YC, Myszka, DG, Segal, D	Cell	2001
11242052	A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis Alnemri, ES, Chai, J, Lee, RA, Hegde, R, Shi, Y, Robbins, PD, Saleh, A, Srinivasula, SM, Fernandes-Alnemri, T, Shiozaki, E, Datta, P	Nature	2001
10972280	Structural and biochemical basis of apoptotic activation by Smac/DIABLO Chai, J, Wang, X, Shi, Y, Wu, JW, Du, C, Kyin, S	Nature	2000