Background
Recently, three different laboratories have identified a molecule, Smac/DIABLO, which binds with inhibitor of apoptosis proteins (IAPs) and neutralizes IP inhibition of effector caspases. Multiple IAP molecules, including c-IAP1, c-IAP2, XIAP, and survivin are able to bind Smac. Smac/DIABLO is a mitochondrial protein, which is released into cytosol during apoptosis. The function of Smac is similar to that of Drosophila apoptosis activating proteins Reaper, Hid and Grim, which have been proposed to function by neutralizing the activity of IAPs. Smac promotes caspase-3 and caspase-9 activation by removing inhibitors rather than directly acting on Apaf-1, procaspases, and cytochrome c. The full-length cDNA of Smac encodes an open reading frame of 239 amino acids, predicting a protein with a molecular weight of 27 kDa. However, the mature protein purified from HeLa cells is only about 25 kDa (3).

Antigen
This rabbit polyclonal antibody was developed against two synthetic peptides corresponding to amino acids 199 to 212 and amino acids 226 to 239 of human Smac (Genbank accession no. AAF87716).

Genebank Info (Protein)
NP_620308

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Reference
1. Du C, et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102 (1): 33-42 (2000).
2. Chai J, et al. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406 (6798): 855-862 (2000).
3. Srinivasula SM, et al. Molecular determinants of the Caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway. J. Biol. Chem. Aug 18 [epub ahead of print] (2000).

Product Citations
1. Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells. Jenq-Chang Lee, Chao-Hung Lee, Chun-Li Su, Chung-Wei Huang, Hsiao-Sheng Liu, Chun-Nan Lin, and Shen-Jeu Won. Carcinogenesis, 26: 1716-1730 (2005). First published on line, May 2005; 10.1093/carcin/bgi133.   
2. Phospholipid Scramblase 3 Controls Mitochondrial Structure, Function, and Apoptotic Response.  Jihua Liu, Qiang Dai, Jun Chen, David Durrant, Angela Freeman, Tong Liu, Douglas Grossman and Ray M. Lee. Molecular Cancer Research 1:892-902 (2003).
3. Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas. Nam Jin Yoo, et al. Apmis (Acta Pathologica, Microbiologica et Immunologica Scandinavica) Volume 111 (3): 382 (2003).
4. SMAC Negatively Regulates the Anti-apoptotic Activity of Melanoma Inhibitor of Apoptosis (ML-IAP).  Domagoj Vucic, Kurt Deshayes, Heidi Ackerly, Maria Teresa Pisabarro, Saloumeh Kadkhodayan, Wayne J. Fairbrother, and Vishva M. Dixit. J. Biol. Chem, 277: 12275– 12279 (2002).
5. Involvement of Proapoptotic Molecules Bax and Bak in Tumor Necrosis Factorrelated Apoptosis-inducing Ligand (TRAIL)-induced Mitochondrial Disruption and Apoptosis: Differential Regulation of Cytochrome c and Smac/DIABLO Release. Karthikeyan Kandasamy, Srinivasa M. Srinivasula, Emad S. Alnemri, Craig B. Thompson, Stanley J. Korsmeyer, Joseph L. Bryant, and Rakesh K. Srivastava. CANCER RESEARCH 63, 1712-1721 (2003).
6. Phospholipid Scramblase 3 Controls Mitochondrial Structure, Function, and Apoptotic Response. Jihua Liu, Qiang Dai, Jun Chen, David Durrant, Angela Freeman, Tong Liu, Douglas Grossman and Ray M. Lee. Molecular Cancer Research 1:892-902 (2003).
7. Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas. NAM JIN YOO, HONG SUG KIM, SU YOUNG KIM, WON SANG PARK, CHO HYUN PARK, HAE MYUNG JEON, EUN SUN JUNG, JUNG YOUNG LEE1 and SUG HYUNG LEE. Apmis (Acta Pathologica, Microbiologica et Immunologica Scandinavica) Volume 111 (3): 382 (2003).
8. Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells. Tong Liu, Brook Brouha, Douglas Grossman. Oncogene 23, 39-48 (2004).
9. PR39 Inhibits Apoptosis in Hypoxic Endothelial Cells. Role of Inhibitor Apoptosis Protein-2. Jiaping Wu, Cherie Parungo, Guifu Wu, Peter M. Kang, Roger J. Laham, Frank W. Sellke, Michael Simons, and Jian Li. Circulation, Mar 2004; 10.1161/01.CIR.0000124067.35915.E0.
10. p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas. Jian-Zhong Qin, Lawrence Stennett, Patricia Bacon, Barbara Bodner, Mary J.C. Hendrix, Richard E.B. Seftor, Elisabeth A. Seftor, Naira V. Margaryan, Pamela M. Pollock, Amy Curtis, Jeffrey M. Trent, Frank Bennett, Lucio Miele, and Brian J. Nickoloff. Mol. Cancer Ther.,  3: 895-902 (2004).
11. Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. Ping Hu, Zhang Han, Anthony D. Couvillon, and John H. Exton. J. Biol. Chem., Aug 2004; 10.1074/jbc.M407700200
12. 7-Ketocholesterol-induced apoptosis: Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways. Arnaud Berthier, Stéphanie Lemaire-Ewing, Céline Prunet, Thomas Montange, Anne Vejux, Jean Paul Pais de Barros , Serge Monier, Philippe Gambert, Gérard Lizard and Dominique Néel. FEBS Journal 272: 3093-3104 (2005).
13. Proteasome Inhibitors Trigger NOXA-Mediated Apoptosis in Melanoma and Myeloma Cells. Jian-Zhong Qin, Jeffrey Ziffra, Lawrence Stennett, Barbara Bodner, Brian K. Bonish, Vijaya Chaturvedi, Frank Bennett, Pamela M. Pollock, Jeffrey M. Trent, Mary J.C. Hendrix, Paola Rizzo, Lucio Miele, and Brian J. Nickoloff. Cancer Res., 65: 6282-6293 (2005).
14. Activation of Dual Apoptotic Pathways in Human Melanocytes and Protection by Survivin. Tong Liu, Diana Biddle, Adrianne N Hanks, Brook Brouha, Hui Yan, Ray M Lee, Sancy A Leachman and Douglas Grossman. Journal of Investigative Dermatology advance online publication 25 May 2006; doi: 10.1038/sj.jid.5700381
15. Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas. Ren Y, N Akyurek, E Schlette, GZ Rassidakis, LJ Medeiros. Human Pathology 37:1407-1413 (2006). (IHC-paraffin) (WB)
16. Caspase-8 is activated by cathespin D initiating neutrophil apoptosis during the resolution of inflammation. Conus S, R Perozzo, T Reinheckel, C Peters, L Scapozza, S Yousefi, H Simon. JEM doi: 10.1084/jem.20072152 (2008). IF (confocal microscopy on human neutrophils), Fig. 2B.
17. Downregulation of Smac/DIABLO Expression in Renal Cell Carcinoma and Its Prognostic Significance. Yoichi Mizutani, Hiroyuki Nakanishi, Kosuke Yamamoto, Yong Nan Li, Hiroki Matsubara, Kazuya Mikami, Koji Okihara, Akihiro Kawauchi, Benjamin Bonavida, and Tsuneharu Miki. J. Clin. Oncol., 23: 448-454 (2005).