Apoptosis, or programmed cell death, is a common property of all multicellular organisms. The current dogma of apoptosis suggests that the components of the core cell-death machinery are integral to cells and widely conserved across species. Caspases, a family of cysteinyl aspartate-specific proteases, are integral components of the cell death machinery (reviewed in Siegal, 2006; and Lavrik et al, 2005). They play a central role in the initiation and execution of apoptotic cell death and in inflammation. Caspases are typically divided into 3 major groups, depending on the structure of their prodomain and their function. Group 1: inflammatory caspases (caspases 1, 4, 5, 11, 12, 14). Group II: initiator of apoptosis caspases (caspases 2, 8, 9). Group II: effector caspases (caspases 3, 6, 7). Caspases are constitutively expressed in almost all cell types as inactive proenzymes (zymogens: enzyme precursors which require a biochemical change to become active enzymes) that are processed and activated in response to a variety of pro-apoptotic or inflammatory stimuli. The procaspases (32-56kD) contain four domains: an N-terminal prodomain (2-25kD), a large subunit (p20: 17-21kD), a small subunit (p10: 10-13kD) and a short linker region between the large and small subunits. Caspase activation involves proteolytic processing of the proenzyme at specific aspartate residues between the domains. This results in removal of the prodomain as well as the linker region and formation of a heterodimer containing one large and one small subunit (p20-p10). The active caspase is a tetramer composed of two heterodimers (p202-p102). Active caspases mediate cell death and inflammation through cleavage of particular cellular substrates that are involved in these processes. Caspase-10 is a 455aa protein. However, caspase-10 produces, by alternative splicing, at least 12 different transcripts, all with introns, putatively encoding at least 11 different protein isoforms. For example, human caspase-10a is a 479aa protein, and human caspase-10d is a 522aa protein. The transcripts appear to differ by truncation of the 3' end, presence or absence of 6 cassette exons, or common exons with different boundaries, because an internal intron is not always spliced out. Caspase-10 gene mutations or polymorphisms have been associated with a number of diseases including type II autoimmune lymphoproliferative syndrome, non-Hiodgkin's lymphoma, and gastric cancer. It is thought that some mutations of the caspase-10 gene may lead to the loss of its apoptotic function, thereby contributing to the pathogenesis of some diseases.
Applications:
Suitable for use in Western Blot, Immunohistochemistry and Immunoprecipitation. Other applications not tested.
Recommended Dilution:
Western Blot: 1:1000-1:2000
Immunohistochemistry (formalin fixed paraffin embedded): 1:1000-1:5000
Immunoprecipitation: 1:50-1:200
Immunohistochemistry: Frozen
Optimal dilutions to be determined by the researcher.
Positive Control:
CNS spleen, lymphoid, CA cell lines
Storage and Stability:
May be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
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