Caspase-3/Sandbox

Caspases are cysteine aspartic acid proteases that are crucial for the initiation (e.g. caspase-8, -9, -10) and execution (e.g. caspase-3, -6, -7) of apoptosis (Degterev, Boyce et al. 2003) through cleavage of death substrates, such as the BH3 domain-only protein BID by caspase-8 (Li, Zhu et al. 1998) and inhibitor of caspase-activated deoxyribonuclease (ICAD) by caspase-3 (Enari, Sakahira et al. 1998; Sakahira, Enari et al. 1998). It has become appreciated more recently that caspase activity, specifically caspase-8, is also required for T cell growth (Alam, Cohen et al. 1999; Kennedy, Kataoka et al. 1999; Misra, Jelley-Gibbs et al. 2005), and that the location and level of active caspases within cells may be a key determinant of survival or death (Misra, Russell et al. 2007; Koenig, Russell et al. 2008). We have previously observed that murine αβ T cells bearing high levels of caspase activity manifest increased rates of both cell growth and cell death (Dohrman, Russell et al. 2005).

Structure & FunctionStructure & Function

StructureStructure

(Structural Description) (highlighting domains, folds and/or motifs) This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how it goes.

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spinqualitylabelsall models PDB ID 2psm Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2psm, resolution 2.19Å ()
Ligands:
Gene:	Il15 (Mus musculus), Il15ra (Mus musculus)
Structural annotation: Resources: InterPro : Ipr003443, Ipr016060, Ipr015486, Ipr000436 Pfam : PF02372, PF00084 UniProt : P48346, Q60819
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB, TOPSAN
Coordinates:	save as pdb, mmCIF, xml

FunctionFunction

(Structural insights into its function)

Evolutionarily Related ProteinsEvolutionarily Related Proteins

Proteins + (Links to evolutionarily related proteins) example IL-2, IL-7

Solved StructuresSolved Structures

(Links to available structures) 3KJF 3ITN 3H0E 3GJQ, 3GJR, 3GJS, 3GJT 3EDQ 3DEH, 3DEI, 3DEJ, 3DEK 2CNK, 2CNL, 2CNN, 2CNO, 2CDR 2J30, 2J31, 2J32, 2J33 2C1E, 2C2K, 2C2M, 2C2O 2H51 2H5J 2H65 2DKO, 2CJX, 2CJY 1RE1 1RHJ, 1RHK, 1RHM, 1RHQ, 1RHR, 1RHU 1NME, 1NMQ, 1NMS 1CP3 1PAU 1I3O 1QX3

References & NotesReferences & Notes

Alam, A., L. Y. Cohen, et al. (1999). "Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells." J Exp Med 190(12): 1879-90.

Aouad, S. M., L. Y. Cohen, et al. (2004). "Caspase-3 is a component of Fas death-inducing signaling complex in lipid rafts and its activity is required for complete caspase-8 activation during Fas-mediated cell death." J Immunol 172(4): 2316-23.

Budd, R. C. (2001). "Activation-induced cell death." Curr Opin Immunol 13(3): 356-62.

Degterev, A., M. Boyce, et al. (2003). "A decade of caspases." Oncogene 22(53): 8543-67.

Dohrman, A., J. Q. Russell, et al. (2005). "Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8." J Immunol 175(1): 311-8.

Enari, M., H. Sakahira, et al. (1998). "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD." Nature 391(6662): 43-50.

Kennedy, N. J., T. Kataoka, et al. (1999). "Caspase activation is required for T cell proliferation." J Exp Med 190(12): 1891-6.

Koenig, A., J. Q. Russell, et al. (2008). "Spatial differences in active caspase-8 defines its role in T-cell activation versus cell death." Cell Death Differ 15(11): 1701-11.

Li, H., H. Zhu, et al. (1998). "Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis." Cell 94(4): 491-501.

Misra, R. S., D. M. Jelley-Gibbs, et al. (2005). "Effector CD4+ T cells generate intermediate caspase activity and cleavage of caspase-8 substrates." J Immunol 174(7): 3999-4009.

Misra, R. S., J. Q. Russell, et al. (2007). "Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation." J Biol Chem 282(27): 19365-74.

Sakahira, H., M. Enari, et al. (1998). "Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis." Nature 391(6662): 96-9.

Vincent, M. S., K. Roessner, et al. (1996). "Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis." J Exp Med 184(6): 2109-17.

Wesselborg, S., O. Janssen, et al. (1993). "Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells." J Immunol 150(10): 4338-45.