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Gene Review

Diablo  -  diablo homolog (Drosophila)

Mus musculus

Synonyms: 0610041G12Rik, 1700006L01Rik, AU040403, Diablo homolog, mitochondrial, Direct IAP-binding protein with low pI, ...
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Disease relevance of Diablo


High impact information on Diablo

  • Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons [5].
  • Second mitochondria-derived activator of caspases (Smac) promotes apoptosis via activation of caspases [2].
  • Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM) [2].
  • In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function [6].
  • We have produced monoclonal antibodies specific for Diablo and have used these to examine its tissue distribution and subcellular localization in healthy and apoptotic cells [7].

Biological context of Diablo


Anatomical context of Diablo


Associations of Diablo with chemical compounds

  • Supporting this idea, the cytosolic release of the mitochondrial proteins SMAC/DIABLO and cytochrome c (Cyt c) was observed, with an initial limited leakage occurring during the first 30 min of L-glutamine deprivation, followed by a greater release after 60 min [15].
  • In addition, TNF increased the mRNA and protein expression of Smac/Diablo [1].
  • The mitochondrial pathway was not activated during paracetamol-induced apoptosis; there was no dissipation of mitochondrial potential or release of apoptogenic factors such as cytochrome c or Smac/DIABLO [16].
  • Resveratrol pretreatment also resulted in (1) reversal of UV-B-mediated decrease of Smac/DIABLO, and (2) enhancement of UV-B-mediated induction of apoptosis, in mouse skin [17].

Regulatory relationships of Diablo


Other interactions of Diablo

  • In conclusion, mitochondrial activation by Bid is required for reversing the IAP inhibition through Smac release [13].
  • Smac was released from mitochondria early following Fas activation and was competitively bound to the IAPs to reverse their effects [13].
  • We report here that Abeta(25-35), a cytotoxic fragment of Abeta, induced translocation of the apoptosis regulator termed second-mitochondria-derived activator of caspase (Smac) from the intramembranous compartment of the mitochondria to the cytosol 24 hr after exposure [18].
  • In contrast, neither adenylate kinase nor Smac/DIABLO was released from isolated rat brain mitochondria via BAK or BAX [19].

Analytical, diagnostic and therapeutic context of Diablo


  1. Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure. Justo, P., Sanz, A., Lorz, C., Gómez-Garre, D., Mezzano, S., Egido, J., Ortiz, A. Kidney Int. Suppl. (2003) [Pubmed]
  2. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Chauhan, D., Neri, P., Velankar, M., Podar, K., Hideshima, T., Fulciniti, M., Tassone, P., Raje, N., Mitsiades, C., Mitsiades, N., Richardson, P., Zawel, L., Tran, M., Munshi, N., Anderson, K.C. Blood (2007) [Pubmed]
  3. Interaction between XIAP and Smac/DIABLO in the mouse brain after transient focal cerebral ischemia. Saito, A., Hayashi, T., Okuno, S., Ferrand-Drake, M., Chan, P.H. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  4. Subcellular localization of a promoter and an inhibitor of apoptosis (Smac/DIABLO and XIAP) during brain ischemia/reperfusion. Shibata, M., Hattori, H., Sasaki, T., Gotoh, J., Hamada, J., Fukuuchi, Y. Neuroreport (2002) [Pubmed]
  5. Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. Potts, P.R., Singh, S., Knezek, M., Thompson, C.B., Deshmukh, M. J. Cell Biol. (2003) [Pubmed]
  6. Generation and characterization of Smac/DIABLO-deficient mice. Okada, H., Suh, W.K., Jin, J., Woo, M., Du, C., Elia, A., Duncan, G.S., Wakeham, A., Itie, A., Lowe, S.W., Wang, X., Mak, T.W. Mol. Cell. Biol. (2002) [Pubmed]
  7. Tissue distribution of Diablo/Smac revealed by monoclonal antibodies. Tikoo, A., O'Reilly, L., Day, C.L., Verhagen, A.M., Pakusch, M., Vaux, D.L. Cell Death Differ. (2002) [Pubmed]
  8. Oxidative stress is associated with XIAP and Smac/DIABLO signaling pathways in mouse brains after transient focal cerebral ischemia. Saito, A., Hayashi, T., Okuno, S., Nishi, T., Chan, P.H. Stroke (2004) [Pubmed]
  9. Exogenous smac induces competence and permits caspase activation in sympathetic neurons. Deshmukh, M., Du, C., Wang, X., Johnson, E.M. J. Neurosci. (2002) [Pubmed]
  10. IFN-gamma induces the apoptosis of WEHI 279 and normal pre-B cell lines by expressing direct inhibitor of apoptosis protein binding protein with low pI. Yoshikawa, H., Nakajima, Y., Tasaka, K. J. Immunol. (2001) [Pubmed]
  11. Divergence of the apoptotic pathways induced by 4-hydroxynonenal and amyloid beta-protein. Rabacchi, S.A., Friedman, W.J., Shelanski, M.L., Troy, C.M. Neurobiol. Aging (2004) [Pubmed]
  12. MEKK1-induced apoptosis is mediated by Smac/Diablo release from the mitochondria. Mendoza, F.J., Henson, E.S., Gibson, S.B. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release of Smac in Fas-mediated hepatocyte apoptosis. Li, S., Zhao, Y., He, X., Kim, T.H., Kuharsky, D.K., Rabinowich, H., Chen, J., Du, C., Yin, X.M. J. Biol. Chem. (2002) [Pubmed]
  14. Expression of Smac/DIABLO in mouse preimplantation embryos and its correlation to apoptosis and fragmentation. Honda, Y., Tanikawa, H., Fukuda, J., Kawamura, K., Sato, N., Sato, T., Shimizu, Y., Kodama, H., Tanaka, T. Mol. Hum. Reprod. (2005) [Pubmed]
  15. Rapid induction of the intrinsic apoptotic pathway by L-glutamine starvation. Paquette, J.C., Guérin, P.J., Gauthier, E.R. J. Cell. Physiol. (2005) [Pubmed]
  16. Paracetamol-induced renal tubular injury: a role for ER stress. Lorz, C., Justo, P., Sanz, A., Subirá, D., Egido, J., Ortiz, A. J. Am. Soc. Nephrol. (2004) [Pubmed]
  17. Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in survivin. Aziz, M.H., Afaq, F., Ahmad, N. Photochem. Photobiol. (2005) [Pubmed]
  18. Amyloid-beta induces Smac release via AP-1/Bim activation in cerebral endothelial cells. Yin, K.J., Lee, J.M., Chen, S.D., Xu, J., Hsu, C.Y. J. Neurosci. (2002) [Pubmed]
  19. Two pathways for tBID-induced cytochrome c release from rat brain mitochondria: BAK- versus BAX-dependence. Brustovetsky, N., Dubinsky, J.M., Antonsson, B., Jemmerson, R. J. Neurochem. (2003) [Pubmed]
  20. Role of Smac/DIABLO in hydrogen peroxide-induced apoptosis in C2C12 myogenic cells. Jiang, B., Xiao, W., Shi, Y., Liu, M., Xiao, X. Free Radic. Biol. Med. (2005) [Pubmed]
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