Diablo

Summary

Gene Symbol: Diablo
Description: diablo, IAP-binding mitochondrial protein
Alias: 0610041G12Rik, 1700006L01Rik, AU040403, Smac, diablo homolog, mitochondrial, direct IAP binding protein with low PI, direct IAP-binding protein with low pI, second mitochondria-derived activator of caspase
Species: mouse
Products:     Diablo

Top Publications

  1. Verhagen A, Ekert P, Pakusch M, Silke J, Connolly L, Reid G, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000;102:43-53 pubmed
    ..DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the ..
  2. Mendoza F, Henson E, Gibson S. MEKK1-induced apoptosis is mediated by Smac/Diablo release from the mitochondria. Biochem Biophys Res Commun. 2005;331:1089-98 pubmed
    ..Herein, we determined that overexpression of MEKK1 causes mitochondrial Smac/Diablo release correlating with MEKK1-induced apoptosis...
  3. Hegde R, Srinivasula S, Zhang Z, Wassell R, Mukattash R, Cilenti L, et al. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem. 2002;277:432-8 pubmed
    ..Like mature Smac (also known as Diablo), mature Omi contains a conserved IAP-binding motif (AVPS) at its N terminus, which is exposed after processing of ..
  4. Martins L, Morrison A, Klupsch K, Fedele V, Moisoi N, Teismann P, et al. Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol Cell Biol. 2004;24:9848-62 pubmed
    ..conclusion is reinforced by the finding that simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived from them...
  5. Wang X, Zhu C, Wang X, Hagberg H, Korhonen L, Sandberg M, et al. X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia-ischemia. Neurobiol Dis. 2004;16:179-89 pubmed
    ..XIAP was colocalized with XAF-1, Smac, and HtrA2 in injured neurons after hypoxia-ischemia (HI)...
  6. Saito A, Hayashi T, Okuno S, Ferrand Drake M, Chan P. Interaction between XIAP and Smac/DIABLO in the mouse brain after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2003;23:1010-9 pubmed
    ..binding to caspases, and is inhibited via binding to the second mitochondria-derived activator of caspase (Smac)/DIABLO to tightly control apoptotic cell death...
  7. Hansen T, Smith D, Nagley P. Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c. Cell Death Differ. 2006;13:1181-90 pubmed
    ..to the mitochondria and activation of the proapoptotic signalling molecule Bax but failed to release Smac/DIABLO from these organelles, judged by both confocal microscopy and Western blotting...
  8. Vaughn A, Deshmukh M. Essential postmitochondrial function of p53 uncovered in DNA damage-induced apoptosis in neurons. Cell Death Differ. 2007;14:973-81 pubmed
  9. Burri L, Strahm Y, Hawkins C, Gentle I, Puryer M, Verhagen A, et al. Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane. Mol Biol Cell. 2005;16:2926-33 pubmed
    b>DIABLO/Smac is a mitochondrial protein that can promote apoptosis by promoting the release and activation of caspases...

More Information

Publications38

  1. Honda Y, Tanikawa H, Fukuda J, Kawamura K, Sato N, Sato T, et al. Expression of Smac/DIABLO in mouse preimplantation embryos and its correlation to apoptosis and fragmentation. Mol Hum Reprod. 2005;11:183-8 pubmed
    ..Recently, second mitochondria-derived activator of caspase/Direct IAP Binding Protein with Low pI (Smac/DIABLO) was identified as a mitochondrial protein that is released into the cytosol during ..
  2. Owens T, Foster F, Valentijn A, Gilmore A, Streuli C. Role for X-linked Inhibitor of apoptosis protein upstream of mitochondrial permeabilization. J Biol Chem. 2010;285:1081-8 pubmed publisher
    ..Membrane-associated XIAP induces mitochondrial outer membrane permeabilization leading to cytochrome c and Smac release, which is dependent on Bax and Bak...
  3. Justo P, Sanz A, Lorz C, Gomez Garre D, Mezzano S, Egido J, et al. Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure. Kidney Int Suppl. 2003;:S52-6 pubmed
    ..However, the mechanisms regulating tubular cell apoptosis are not well understood. Smac/Diablo is a mitochondrial protein that is released to the cytosol during apoptosis, where it blocks the antiapoptotic ..
  4. Fan L, Zhou X, Sweeney W, Wallace D, Avner E, Grantham J, et al. Smac-mimetic-induced epithelial cell death reduces the growth of renal cysts. J Am Soc Nephrol. 2013;24:2010-22 pubmed publisher
    ..death can be achieved by cotreatment with TNF-? and a mimetic of second mitochondria-derived activator of caspase (Smac). Notably, TNF-? accumulates to high levels in ADPKD cyst fluid...
  5. Verhagen A, Silke J, Ekert P, Pakusch M, Kaufmann H, Connolly L, et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem. 2002;277:445-54 pubmed
    ..proteins inhibit caspases, a function counteracted by IAP antagonists, insect Grim, HID, and Reaper and mammalian DIABLO/Smac...
  6. Qiu W, Wang X, Leibowitz B, Liu H, Barker N, Okada H, et al. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci U S A. 2010;107:20027-32 pubmed publisher
    ..Furthermore, deficiency in SMAC, a mitochondrial apoptogenic protein, attenuated the tumor-suppressive effect of sulindac in APC(Min/+) mice by ..
  7. Kim J, Kim S, Kim B, Lee H, Kim I, Yun J, et al. Identification of a novel anti-apoptotic E3 ubiquitin ligase that ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2, and ARTS. J Biol Chem. 2013;288:12014-21 pubmed publisher
    ..AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. However, AREL1 was cytosolic and did not localize to nuclei or mitochondria...
  8. Wiley S, Murphy A, Ross S, van der Geer P, Dixon J. MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity. Proc Natl Acad Sci U S A. 2007;104:5318-23 pubmed
    ..Cardiac mitochondria isolated from mitoNEET-null mice demonstrate a reduced oxidative capacity, suggesting that mito- NEET is an important iron-containing protein involved in the control of maximal mitochondrial respiratory rates. ..
  9. Okada H, Suh W, Jin J, Woo M, Du C, Elia A, et al. Generation and characterization of Smac/DIABLO-deficient mice. Mol Cell Biol. 2002;22:3509-17 pubmed
    The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs)...
  10. Hostager B, Fox D, Whitten D, Wilkerson C, Eipper B, Francone V, et al. HOIL-1L interacting protein (HOIP) as an NF-kappaB regulating component of the CD40 signaling complex. PLoS ONE. 2010;5:e11380 pubmed publisher
    ..In addition to known CD40-interacting proteins, we detected SMAC/DIABLO, HTRA2/Omi, and HOIP/RNF31/PAUL/ZIBRA...
  11. Andree M, Seeger J, Schüll S, Coutelle O, Wagner Stippich D, Wiegmann K, et al. BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella. EMBO J. 2014;33:2171-87 pubmed publisher
    ..During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase-mediated activation of BID...
  12. Perez G, Acton B, Jurisicova A, Perkins G, White A, Brown J, et al. Genetic variance modifies apoptosis susceptibility in mature oocytes via alterations in DNA repair capacity and mitochondrial ultrastructure. Cell Death Differ. 2007;14:524-33 pubmed
    ..c release and a high apoptosis susceptibility, the latter of which is suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of 'normal' mitochondria...
  13. Tikoo A, O Reilly L, Day C, Verhagen A, Pakusch M, Vaux D. Tissue distribution of Diablo/Smac revealed by monoclonal antibodies. Cell Death Differ. 2002;9:710-6 pubmed
    b>Diablo/Smac is a mammalian pro-apoptotic protein that can antagonize the inhibitor of apoptosis proteins (IAPs)...
  14. Shibata M, Hattori H, Sasaki T, Gotoh J, Hamada J, Fukuuchi Y. Subcellular localization of a promoter and an inhibitor of apoptosis (Smac/DIABLO and XIAP) during brain ischemia/reperfusion. Neuroreport. 2002;13:1985-8 pubmed
    We explored the expression of Smac/DIABLO, a newly identified mitochondrial apoptogenic molecule, and X-linked inhibitor of apoptosis protein (XIAP) in the brain subjected to ischemia/reperfusion...
  15. Cheng J, Zhu Y, He S, Lu Y, Chen J, Han B, et al. Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64. Am J Hum Genet. 2011;89:56-66 pubmed publisher
    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...
  16. Hui K, Kanungo A, Elia A, Henderson J. Caspase-3 deficiency reveals a physiologic role for Smac/DIABLO in regulating programmed cell death. Cell Death Differ. 2011;18:1780-90 pubmed publisher
    ..homologue of second mitochondrial-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) has yet to be clearly established in vivo...
  17. Ho A, Li Q, Okada H, Mak T, Zacksenhaus E. XIAP activity dictates Apaf-1 dependency for caspase 9 activation. Mol Cell Biol. 2007;27:5673-85 pubmed
    ..of caspases in response to cytotoxic drugs requires both Apaf-1-induced dimerization of procaspase 9 and Smac/Diablo-mediated sequestration of inhibitors of apoptosis proteins (IAPs)...
  18. Stoka V, Turk V, Bredesen D. Differential regulation of Smac/DIABLO and Hsp-70 during brain maturation. Neuromolecular Med. 2007;9:255-63 pubmed
    ..of brain maturation in CD-1 mice, triggered by two mitochondrial proapoptotic proteins, cytochrome c and Smac/DIABLO, and the pathway's regulation by Hsp-70. Smac/DIABLO and Hsp-70 proteins were upregulated 2-fold and 1...
  19. Petersen S, Wang L, Yalcin Chin A, Li L, Peyton M, Minna J, et al. Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007;12:445-56 pubmed
    A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs...
  20. Galluzzi L, Joza N, Tasdemir E, Maiuri M, Hengartner M, Abrams J, et al. No death without life: vital functions of apoptotic effectors. Cell Death Differ. 2008;15:1113-23 pubmed publisher
  21. Ni H, Chen X, Shi Y, Liao Y, Beg A, Fan J, et al. Genetic delineation of the pathways mediated by bid and JNK in tumor necrosis factor-alpha-induced liver injury in adult and embryonic mice. J Biol Chem. 2009;284:4373-82 pubmed publisher
    ..This work defined both linear and parallel relationships of Bid and JNK in TNFalpha-induced hepatocyte apoptosis and liver injury. ..
  22. Potts P, Singh S, Knezek M, Thompson C, Deshmukh M. Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. J Cell Biol. 2003;163:789-99 pubmed
    ..Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons...
  23. Jiang B, Xiao W, Shi Y, Liu M, Xiao X. Role of Smac/DIABLO in hydrogen peroxide-induced apoptosis in C2C12 myogenic cells. Free Radic Biol Med. 2005;39:658-67 pubmed
    Smac/DIABLO was recently identified as a protein released from mitochondria in response to apoptotic stimuli which promotes apoptosis by antagonizing inhibitors of apoptosis proteins...
  24. Qiu W, Liu H, Sebastini A, Sun Q, Wang H, Zhang L, et al. An apoptosis-independent role of SMAC in tumor suppression. Oncogene. 2013;32:2380-9 pubmed publisher
    Reduced expression of the pro-apoptotic protein SMAC (second mitochondria-derived activator of caspase) has been reported to correlate with cancer progression, while its significance and underlying mechanisms are poorly understood...
  25. Kang B, Xia F, Pop R, Dohi T, Socolovsky M, Altieri D. Developmental control of apoptosis by the immunophilin aryl hydrocarbon receptor-interacting protein (AIP) involves mitochondrial import of the survivin protein. J Biol Chem. 2011;286:16758-67 pubmed publisher
    ..Therefore, an AIP-Tom20 recognition contributes to cell survival in development and cancer by mediating the mitochondrial import of survivin. ..
  26. Kandasamy K, Srinivasula S, Alnemri E, Thompson C, Korsmeyer S, Bryant J, et al. Involvement of proapoptotic molecules Bax and Bak in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced mitochondrial disruption and apoptosis: differential regulation of cytochrome c and Smac/DIABLO release. Cancer Res. 2003;63:1712-21 pubmed
    ..Unlike cytochrome c release, TRAIL-induced Smac/DIABLO release was blocked in Bid(-/-), Bax(-/-), Bak(-/-), or DKO MEFs, suggesting the differential regulation of these ..
  27. Yoon K, Jang H, Lee S. Direct interaction of Smac with NADE promotes TRAIL-induced apoptosis. Biochem Biophys Res Commun. 2004;319:649-54 pubmed
    ..We screened for Smac/DIABLO-binding protein for further understanding of Smac-mediated apoptosis...
  28. Rardin M, Wiley S, Murphy A, Pagliarini D, Dixon J. Dual specificity phosphatases 18 and 21 target to opposing sides of the mitochondrial inner membrane. J Biol Chem. 2008;283:15440-50 pubmed publisher
    ..This work rigorously demonstrates the unique location of two highly similar DSPs on opposing sides of the mitochondrial inner membrane...
  29. Li S, Zhao Y, He X, Kim T, Kuharsky D, Rabinowich H, et al. Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release of Smac in Fas-mediated hepatocyte apoptosis. J Biol Chem. 2002;277:26912-20 pubmed
    ..This block could be overcome in wild-type mice by two mechanisms. Smac was released from mitochondria early following Fas activation and was competitively bound to the IAPs to reverse ..