CASP6 Research Reagents

Caspase-6 is a protein in humans that is encoded by CASP6 gene. Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.

The following CASP6 reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

CASP6 Antibodies

CASP6 Antibodies for Homo sapiens (Human)

CASP6 Antibodies for Mus musculus (Mouse)

CASP6 Proteins

CASP6 Proteins for Homo sapiens (Human)

CASP6 Proteins for Mus musculus (Mouse)

CASP6 Proteins for Rattus norvegicus (Rat)

CASP6 Proteins for Bos taurus (Bovine)

CASP6 Background

The CASP6 gene encodes caspase-6, an effector caspase that is responsible for apoptosis execution [1]. Caspase-6 is expressed as a dimeric zymogen containing a short prodomain, a large subunit carrying the Cys 163 catalytic cysteine (p20), a small subunit (p10), and an inter‐subunit linker [2]. Although caspase-6 respectively shares partial sequence similarity with caspase-3 and caspase-7, it has several distinctive features. The substrate specificity of caspase-6 is similar to the initiators such as caspase-8 and caspase-9 rather than that of caspase-3 and caspase-7 [11]. The pro-domain of caspase-6 inhibits its self-activation in vivo [3] and in vitro [4]. Caspase-6 is activated by proteolytic processing at the prodomain Asp 23, and both sides of the intersubunit linker Asp 179 (caspase-3 cleavage) and Asp 193 (self-activated cleavage) [5]. Caspase-6 is often activated by caspase-3 rather than initiator caspases during apoptosis [6][7], but it can also be activated in the absence of caspase-3 activity [8][9]. When stimulated by caspase-1, caspase-6 is also associated with the inflammatory pathway [10]. Active caspase-6 is abundant in the neuropathological lesions of Alzheimer's disease [12], Huntington's disease [13], and Parkinson's disease [14]. The physiological outcomes in these neurological disorders are influenced through the cleavage of the neuronal substrates by caspase-6, so it is promising to improve neurodegeneration therapy through caspase-6-targeted therapeutics.

[1] Boatright KM, Salvesen GS Mechanisms of caspase activation [J]. Curr Opin Cell Biol. 2003 Dec; 15(6):725-31.
[2] Nicholson DW Caspase structure, proteolytic substrates, and function during apoptotic cell death [J]. Cell Death Differ, 1999, 6: 1028-1042.
[3] Klaiman G, Champagne N, et al. Self-activation of Caspase-6 in vitro and in vivo: Caspase-6 activation does not induce cell death in HEK293T cells [J]. Biochim Biophys Acta, 2009, 1793:592-601.
[4] Klaiman G, Champagne N, et al. Self-activation of Caspase-6 in vitro and in vivo: Caspase-6 activation does not induce cell death in HEK293T cells [J]. Biochim Biophys Acta 2009, 1793:592-601.
[5] Srinivasula SM, Fernandes‐Alnemri T, et al. The Ced‐3/interleukin 1beta converting enzyme‐like homolog Mch6 and the lamin‐cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32 [J]. J Biol Chem, 1996, 271: 27099-27106.
[6] Slee EA et al. Ordering the cytochrome c‐initiated caspase cascade: hierarchical activation of caspases‐2, ‐3, ‐6, ‐7, ‐8, and ‐10 in a caspase‐9‐dependent manner [J]. J Cell Biol 1999, 144: 281-292.
[7] Simon DJ, et al. A caspase cascade regulating developmental axon degeneration [J]. J Neurosci 2012, 32:17540-17553.
[8] LeBlanc A, Liu H, et al. Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease [J]. J Biol Chem 1999, 274:23426-23436.
[9] Allsopp TE, McLuckie J, et al. Caspase 6 activity initiates caspase 3 activation in cerebellar granule cell apoptosis [J]. Cell Death Differ 2000, 7: 984-993.
[10] Guo H, et al. Caspase-1 activation of caspase-6 in human apoptotic neurons [J]. Cell Death Differ 2006, 13:285-292.
[11] Thornberry NA et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis [J]. J Biol Chem 1997, 272: 17907-17911.
[12] Guo H, Albrecht S, et al. Active caspase‐6 and caspase‐6‐cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer’s disease [J]. Am J Pathol 2004, 165: 523-531.
[13] Aharony I, et al. A Huntingtin-based peptide inhibitor of caspase-6 provides protection from mutant Huntingtin-induced motor and behavioral deficits. [J]. Hum Mol Genet 2015,24:2604-2614.
[14] Giaime E, et al. Loss of function of DJ-1 triggered by Parkinson's disease-associated mutation is due to proteolytic resistance to caspase-6 [J]. Cell Death Differ, 2010, 17:158-169.

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