Diablo Homolog (SMAC)

Apoptosis is an essential processes required for normal development and homeostasis of all metazoan organisms. Second Mitochondria-Derived Activator of Caspases (Smac) or Direct IAP Binding Protein with low isoelectric point, pI (Diablo) is a proapoptogenic mitochondrial protein that is released to the cytosol in response to diverse apoptotic stimuli, including commonly used chemotherapeutic drugs. The current knowlege about structure and function of Smac/Diablo during programmed cell death, both in mitochondrial and receptor pathways are presented. It has been shown that Diablo mainly interacts with IAPs in the cytochrome c/Apaf-1/caspase-9 pathway, and promotes apoptosis. Diablo is released from the mitochondria into the cytosol occurring downstream of cytochrome c release in response to apoptotic stimuli such as irradiation, DNA damage or cytotoxic drugs. In the cytosol, Smac/Diablo interacts and antagonizes inhibitors of apoptosis proteins (IAPs), thus allowing the activation of caspases and apoptosis. This activity has prompted the synthesis of peptidomimetics that could potentially be used in cancer therapy. The role of Smac/DIABLO in colorectal carcinogenesis is ill defined. Data continues to accumulate to suggest that decreased levels of Smac/DIABLO may be important in chemoradiation-resistance to apoptosis in advanced colon cancer.

Diablo Homolog (SMAC) Related Areas

Cancer>>Apoptosis>>Inhibitor of Apoptosis (IAP)>>SMAC/Diablo

Diablo Homolog (SMAC) Alternative Names

SMAC, DIABLO, hCG_1782202, DIABLO-S, FLJ10537, FLJ25049, SMAC [Homo sapiens]

Smac, Diablo , 0610041G12Rik, 1700006L01Rik, AU040403 [Mus musculus]

Summaries for Diablo Homolog (SMAC)

Entrez Gene summary for Diablo Homolog (SMAC):

This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and it moderates the caspase inhibition of IAPs. Multiple polyadenylation sites have been found for this gene. Four alternatively spliced transcript variants have been described for this gene, with two of them encoding different isoforms and the other two probably not encoding a protein

OMIM - description for Diablo Homolog (SMAC):

Wikipedia summary for Diablo Homolog (SMAC):

Diablo homolog, mitochondrial is a protein that in humans is encoded by the DIABLO gene (direct IAP binding protein with low pI).DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC.

Human Diablo Homolog (SMAC) Protein General Information

 

• Protein names: Recommended name: Diablo homolog, mitochondrial
• Sequence length: 239 AA.
• Domain: The mature N-terminus mediates interaction with XIAP/BIRC4.
• Post-translational modification: Ubiquitinated by BIRC7/livin
• Subunit structure: Homodimer. Interacts with NGFRAP1/BEX3 By similarity. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2, XIAP/BIRC4, BIRC6/bruce and BIRC7/livin. Interacts with the monomeric and dimeric form of BIRC5/survivin
• Subcellular location: Mitochondrion. Note: Released into the cytosol when cells undergo apoptosis.
• Tissue specificity: Ubiquitously expressed with highest expression in testis. Expression is also high in heart, liver, kidney, spleen, prostate and ovary. Low in brain, lung, thymus and peripheral blood leukocytes. Isoform 3 is ubiquitously expressed.
• Involvement in disease: Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:614152]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.

General information above from UniProt

Function for Diablo Homolog (SMAC) Protein

UniProtKB:

Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance

Genatlas:

• Diablo Homolog (SMAC) promote apoptosis by binding to caspase inhibitors of the IAP family (BIRCS) and preventing them from inhibiting caspases
• Diablo Homolog (SMAC) activate caspases in the cytochrome C/APAF1/CASP9 pathway
• Diablo Homolog (SMAC) is involved in TNF-mediated CASP8 activation and apoptosis
• Diablo Homolog (SMAC) plays an essential role in the apoptosis induced by non-steroidal anti-inflammatory drugs in colon cancer
• IAP-binding protein that is released from mitochondria during apoptosis
• Diablo Homolog (SMAC) potentiates apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activities
• Diablo Homolog (SMAC) plays an obligatory role in the tumor cells during several pathways of apoptosis induction
• mitochondrial apoptogenic protein, mediating the proapoptotic function of BBC3 by regulating BBC3-induced mitochondrial events
• Diablo Homolog (SMAC) plays an important role in executing DNA damage-induced and BBC3-mediated apoptosis and can participates in a feedback amplification loop to promote cytochrome c release and other mitochondrial events in apoptosis

Homology for human Diablo Homolog (SMAC)

• homolog to murine Diablo (85.2pc)
• homolog to rattus Diablo (85.7pc)