Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition
- PMID: 10929711
- DOI: 10.1016/s0092-8674(00)00008-8
Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition
Abstract
We report here the identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis. Mitochondrial import and cleavage of its signal peptide are required for Smac to gain its apoptotic activity. Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases.
Similar articles
-
Apaf-1/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells.J Biol Chem. 2001 Jul 6;276(27):24453-6. doi: 10.1074/jbc.C100074200. Epub 2001 May 16. J Biol Chem. 2001. PMID: 11356822
-
Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein.J Biol Chem. 2003 Dec 26;278(52):52660-72. doi: 10.1074/jbc.M308036200. Epub 2003 Sep 30. J Biol Chem. 2003. PMID: 14523016
-
Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2.EMBO J. 2001 Dec 3;20(23):6627-36. doi: 10.1093/emboj/20.23.6627. EMBO J. 2001. PMID: 11726499 Free PMC article.
-
A structural view of mitochondria-mediated apoptosis.Nat Struct Biol. 2001 May;8(5):394-401. doi: 10.1038/87548. Nat Struct Biol. 2001. PMID: 11323712 Review.
-
Smac/DIABLO and colon cancer.Anticancer Agents Med Chem. 2007 Jul;7(4):467-73. doi: 10.2174/187152007781058631. Anticancer Agents Med Chem. 2007. PMID: 17630921 Review.
Cited by
-
Induction of Mitochondrial Pathways and Endoplasmic Reticulum Stress for Increasing Apoptosis in Ectopic and Orthotopic Neuroblastoma Xenografts.J Cancer Ther. 2011 Jun;2(2):77-90. doi: 10.4236/jct.2011.22009. J Cancer Ther. 2011. PMID: 22468231 Free PMC article.
-
SMAC/Diablo controls proliferation of cancer cells by regulating phosphatidylethanolamine synthesis.Mol Oncol. 2021 Nov;15(11):3037-3061. doi: 10.1002/1878-0261.12959. Epub 2021 May 4. Mol Oncol. 2021. PMID: 33794068 Free PMC article.
-
Control of mitochondrial activity by miRNAs.J Cell Biochem. 2012 Apr;113(4):1104-10. doi: 10.1002/jcb.24004. J Cell Biochem. 2012. PMID: 22135235 Free PMC article. Review.
-
Simultaneous Targeting of Two Master Regulators of Apoptosis with Dual-Action PNA- and DNA-Peptide Conjugates.Bioconjug Chem. 2020 Aug 19;31(8):1928-1937. doi: 10.1021/acs.bioconjchem.0c00284. Epub 2020 Jul 7. Bioconjug Chem. 2020. PMID: 32567853 Free PMC article.
-
A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy.Drug Discov Today. 2016 Jan;21(1):38-47. doi: 10.1016/j.drudis.2015.07.014. Epub 2015 Jul 30. Drug Discov Today. 2016. PMID: 26232549 Free PMC article. Review.
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials