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Caspase 3, apoptosis-related cysteine peptidase
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| PDB rendering based on 1rhk. |
| Available structures: 1cp3, 1gfw, 1i3o, 1nme, 1nmq, 1nms, 1pau, 1qx3, 1re1, 1rhj, 1rhk, 1rhm, 1rhq, 1rhr, 1rhu, 2c1e, 2c2k, 2c2m, 2c2o, 2cdr, 2cjx, 2cjy, 2cnk, 2cnl, 2cnn, 2cno, 2dko, 2h5i, 2h5j, 2h65, 2j30, 2j31, 2j32, 2j33 |
| Identifiers |
| Symbols |
CASP3; CPP32; CPP32B; SCA-1 |
| External IDs |
OMIM: 600636 MGI: 107739 HomoloGene: 37912 |
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| RNA expression pattern |
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More reference expression data
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| Orthologs |
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Human |
Mouse |
| Entrez |
836 |
12367 |
| Ensembl |
ENSG00000164305 |
ENSMUSG00000031628 |
| Uniprot |
P42574 |
Q8BNT4 |
| Refseq |
NM_004346 (mRNA)
NP_004337 (protein) |
XM_991820 (mRNA)
XP_996914 (protein) |
| Location |
Chr 4: 185.79 - 185.81 Mb |
Chr 8: 48.12 - 48.14 Mb |
| Pubmed search |
[1] |
[2] |
Caspase 3 is a caspase protein which interacts with caspase 8 and caspase 9.
This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7, and 9; and the protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein.[1]
Signaling pathway of
TNF-R1. Dashed grey lines represent multiple steps
Interactions
Caspase 3 has been shown to interact with Survivin,[2][3] XIAP,[4][5][6][7][8][9] CFLAR,[10][11] Caspase 8,[12][13] HCLS1,[14][15] Deleted in Colorectal Cancer,[16] TRAF3[17][18] and GroEL.[19][20]
References
Pathways leading to caspase 3 activation. From Harrington et al., 2008
- ^ "Entrez Gene: CASP3 caspase 3, apoptosis-related cysteine peptidase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=836.
- ^ Tamm, I; Wang Y, Sausville E, Scudiero D A, Vigna N, Oltersdorf T, Reed J C (Dec. 1998). "IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs". Cancer Res. (UNITED STATES) 58 (23): 5315-20. ISSN 0008-5472. PMID 9850056.
- ^ Shin, S; Sung B J, Cho Y S, Kim H J, Ha N C, Hwang J I, Chung C W, Jung Y K, Oh B H (Jan. 2001). "An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7". Biochemistry (United States) 40 (4): 1117-23. ISSN 0006-2960. PMID 11170436.
- ^ Suzuki, Y; Nakabayashi Y, Takahashi R (Jul. 2001). "Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (15): 8662-7. doi:10.1073/pnas.161506698. ISSN 0027-8424. PMID 11447297.
- ^ Silke, John; Hawkins Christine J, Ekert Paul G, Chew Joanne, Day Catherine L, Pakusch Miha, Verhagen Anne M, Vaux David L (Apr. 2002). "The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites". J. Cell Biol. (United States) 157 (1): 115-24. doi:10.1083/jcb.200108085. ISSN 0021-9525. PMID 11927604.
- ^ Riedl, S J; Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik S W, Liddington R C, Salvesen G S (Mar. 2001). "Structural basis for the inhibition of caspase-3 by XIAP". Cell (United States) 104 (5): 791-800. ISSN 0092-8674. PMID 11257232.
- ^ Roy, N; Deveraux Q L, Takahashi R, Salvesen G S, Reed J C (Dec. 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. (ENGLAND) 16 (23): 6914-25. doi:10.1093/emboj/16.23.6914. ISSN 0261-4189. PMID 9384571.
- ^ Deveraux, Q L; Takahashi R, Salvesen G S, Reed J C (Jul. 1997). "X-linked IAP is a direct inhibitor of cell-death proteases". Nature (ENGLAND) 388 (6639): 300-4. doi:10.1038/40901. ISSN 0028-0836. PMID 9230442.
- ^ Suzuki, Y; Nakabayashi Y, Nakata K, Reed J C, Takahashi R (Jul. 2001). "X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes". J. Biol. Chem. (United States) 276 (29): 27058-63. doi:10.1074/jbc.M102415200. ISSN 0021-9258. PMID 11359776.
- ^ Shu, H B; Halpin D R, Goeddel D V (Jun. 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity (UNITED STATES) 6 (6): 751-63. ISSN 1074-7613. PMID 9208847.
- ^ Han, D K; Chaudhary P M, Wright M E, Friedman C, Trask B J, Riedel R T, Baskin D G, Schwartz S M, Hood L (Oct. 1997). "MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (21): 11333-8. ISSN 0027-8424. PMID 9326610.
- ^ Guo, Yin; Srinivasula Srinivasa M, Druilhe Anne, Fernandes-Alnemri Teresa, Alnemri Emad S (Apr. 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. (United States) 277 (16): 13430-7. doi:10.1074/jbc.M108029200. ISSN 0021-9258. PMID 11832478.
- ^ Srinivasula, S M; Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri E S (Dec. 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (25): 14486-91. ISSN 0027-8424. PMID 8962078.
- ^ Ruzzene, Maria; Penzo Daniele, Pinna Lorenzo A (May. 2002). "Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells". Biochem. J. (England) 364 (Pt 1): 41-7. ISSN 0264-6021. PMID 11988074.
- ^ Chen, Y R; Kori R, John B, Tan T H (Nov. 2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis". Biochem. Biophys. Res. Commun. (United States) 288 (4): 981-9. doi:10.1006/bbrc.2001.5862. ISSN 0006-291X. PMID 11689006.
- ^ Forcet, C; Ye X, Granger L, Corset V, Shin H, Bredesen D E, Mehlen P (Mar. 2001). "The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (6): 3416-21. doi:10.1073/pnas.051378298. ISSN 0027-8424. PMID 11248093.
- ^ Lee, Z H; Lee S E, Kwack K, Yeo W, Lee T H, Bae S S, Suh P G, Kim H H (Mar. 2001). "Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells". J. Leukoc. Biol. (United States) 69 (3): 490-6. ISSN 0741-5400. PMID 11261798.
- ^ Leo, E; Deveraux Q L, Buchholtz C, Welsh K, Matsuzawa S, Stennicke H R, Salvesen G S, Reed J C (Mar. 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. (United States) 276 (11): 8087-93. doi:10.1074/jbc.M009450200. ISSN 0021-9258. PMID 11098060.
- ^ Samali, A; Cai J, Zhivotovsky B, Jones D P, Orrenius S (Apr. 1999). "Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells". EMBO J. (ENGLAND) 18 (8): 2040-8. doi:10.1093/emboj/18.8.2040. ISSN 0261-4189. PMID 10205158.
- ^ Xanthoudakis, S; Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson D W (Apr. 1999). "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. (ENGLAND) 18 (8): 2049-56. doi:10.1093/emboj/18.8.2049. ISSN 0261-4189. PMID 10205159.
See also
External links
Further reading
- Cohen GM (1997). "Caspases: the executioners of apoptosis.". Biochem. J. 326 ( Pt 1): 1–16. PMID 9337844.
- Roig J, Traugh JA (2001). "Cytostatic p21 G protein-activated protein kinase gamma-PAK.". Vitam. Horm. 62: 167–98. doi:10.1016/S0083-6729(01)62004-1. PMID 11345898.
- Zhao LJ, Zhu H (2005). "Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to drug design.". Curr. Drug Targets Immune Endocr. Metabol. Disord. 4 (4): 265–75. doi:10.2174/1568008043339668. PMID 15578977.
- Le Rouzic E, Benichou S (2006). "The Vpr protein from HIV-1: distinct roles along the viral life cycle.". Retrovirology 2: 11. doi:10.1186/1742-4690-2-11. PMID 15725353.
- Sykes MC, Mowbray AL, Jo H (2007). "Reversible glutathiolation of caspase-3 by glutaredoxin as a novel redox signaling mechanism in tumor necrosis factor-alpha-induced cell death.". Circ. Res. 100 (2): 152–4. doi:10.1161/01.RES.0000258171.08020.72. PMID 17272816.
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PDB Gallery |
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1cp3: CRYSTAL STRUCTURE OF THE COMPLEX OF APOPAIN WITH THE TETRAPEPTIDE INHIBITOR ACE-DVAD-FMC
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1gfw: THE 2.8 ANGSTROM CRYSTAL STRUCTURE OF CASPASE-3 (APOPAIN OR CPP32)IN COMPLEX WITH AN ISATIN SULFONAMIDE INHIBITOR.
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1i3o: CRYSTAL STRUCTURE OF THE COMPLEX OF XIAP-BIR2 AND CASPASE 3
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1nme: Structure of Casp-3 with tethered salicylate
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1nmq: Extendend Tethering: In Situ Assembly of Inhibitors
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1nms: Caspase-3 tethered to irreversible inhibitor
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1pau: CRYSTAL STRUCTURE OF THE COMPLEX OF APOPAIN WITH THE TETRAPEPTIDE ALDEHYDE INHIBITOR AC-DEVD-CHO
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1qx3: Conformational restrictions in the active site of unliganded human caspase-3
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1re1: CRYSTAL STRUCTURE OF CASPASE-3 WITH A NICOTINIC ACID ALDEHYDE INHIBITOR
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1rhj: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A PRYAZINONE INHIBITOR
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1rhk: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A PHENYL-PROPYL-KETONE INHIBITOR
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1rhm: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A NICOTINIC ACID ALDEHYDE INHIBITOR
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1rhq: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR
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1rhr: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A CINNAMIC ACID METHYL ESTER INHIBITOR
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1rhu: CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A 5,6,7 TRICYCLIC PEPTIDOMIMETIC INHIBITOR
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2c1e: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.
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2c2k: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.
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2c2m: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.
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2c2o: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.
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2cdr: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE EPOXIDE INHIBITORS.
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2cjx: EXTENDED SUBSTRATE RECOGNITION IN CASPASE-3 REVEALED BY HIGH RESOLUTION X-RAY STRUCTURE ANALYSIS
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2cjy: EXTENDED SUBSTRATE RECOGNITION IN CASPASE-3 REVEALED BY HIGH RESOLUTION X-RAY STRUCTURE ANALYSIS
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2cnk: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE EPOXIDE INHIBITORS.
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2cnl: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE EPOXIDE INHIBITORS.
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2cnn: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE EPOXIDE INHIBITORS.
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2cno: CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE EPOXIDE INHIBITORS.
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2dko: Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis
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2h5i: Crystal structure of caspase-3 with inhibitor Ac-DEVD-Cho
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2h5j: Crystal strusture of caspase-3 with inhibitor Ac-DMQD-Cho
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2h65: Crystal strusture of caspase-3 with inhibitor Ac-VDVAD-Cho
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