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SMAC

Chr.12 MIM.605219

Friday 24 November 2006

Definition: SMAC/Diablo is a mitochondrial apoptogenic protein. SMAC promotes caspase activation in the cytochrome c/APAF1/CASP9 pathway. Caspase (CSPs) activation is a key regulatory step for apoptosis.

SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs

Cytochrome c (CYCS) (MIM.123970) released from the mitochondrial intermembrane space triggers a major caspase activation cascade. Cytochrome c is located in the mitochondria of all aerobic cells and is involved in the electron transport system that functions in oxidative phosphorylation. It accepts electrons from cytochrome b and transfers them to cytochrome oxidase. In the process, the iron of the heme group, which is identical to that of hemoglobin and myoglobin, shifts from the ferrous to the ferric state.

Upon its release to the cytosol, cytochrome c (CYCS) binds to APAF1 (MIM.602233) in the presence of dATP or ATP. The cytochrome c/APAF1 complex then recruits procaspase-9 (CASP9) (MIM.602234), inducing its autoactivation and leading to the activation of downstream caspases (CSPs).

Proteins of the BCL2 (MIM.603167) families and inhibitor of apoptosis proteins (IAPs) are major regulators of the cytochrome c/APAF1/CASP9 pathway. SMAC promotes caspase activation in this pathway.

Pathology

- Functional Mutation of SMAC/DIABLO, Encoding a Mitochondrial Proapoptotic Protein, Causes Human Progressive Hearing Loss DFNA64. (21722859)

References

- Functional Mutation of SMAC/DIABLO, Encoding a Mitochondrial Proapoptotic Protein, Causes Human Progressive Hearing Loss DFNA64. Cheng J, Zhu Y, He S, Lu Y, Chen J, Han B, Petrillo M, Wrzeszczynski KO, Yang S, Dai P, Zhai S, Han D, Zhang MQ, Li W, Liu X, Li H, Chen ZY, Yuan H. Am J Hum Genet. 2011 Jun 29. PMID: 21722859

- Ren Y, Akyurek N, Schlette E, Rassidakis GZ, Medeiros LJ. Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas.
Hum Pathol. 2006 Nov;37(11):1407-13. PMID: 16949641

- Vischioni B, van der Valk P, Span SW, Kruyt FA, Rodriguez JA, Giaccone G. Expression and localization of inhibitor of apoptosis proteins in normal human tissues. Hum Pathol. 2006 Jan;37(1):78-86. PMID: 16360419