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background:
Caspases are a family of intracellular proteases that mediate cell death and are the principal effectors of apoptosis. Caspase 10 (Mch4, ICE-LAP4, FLICE2) plays an important role in apoptosis induced by a variety of inducers such as TNF alpha and Anti-Fas antibody. It is a large prodomain caspase classified together with caspases 2, 8, and 9 as a signaling caspase. Four isoforms of caspase 10 (caspase 10a, 10b, 10c, and 10d) having the same prodomain but different mature large and small subdomain, have been described. Caspase 10 contains two death domains (DED) involved in linking to the death effector domain of the adapter protein FADD and recruiting the complex to TNFR1 and Fas. The inactive procaspase 10 is variably expressed in many tissues and cell lines as a cytosolic protein. The mature form of caspase 10 comprises two subunits, p23/p17 (splice isoforms) and p12. Interestingly, a caspase 9- dependent processing of caspase 10 by caspase 6 in cell-free extracts has recently been suggested. Caspase 10 can cleave and activate caspases 3, 4, 6, 7, 8, and 9. This is followed by cleavage of numerous key proteins, including the nuclear protein PARP.
Function:
Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase-3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC.
Subunit:
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 23/17 kDa (p23/17) (depending on the splicing events) and a 12 kDa (p12) subunit (By similarity). Self-associates. Interacts with FADD and CASP8. Found in a Fas signaling complex consisting of FAS, FADD, CASP8 and CASP10.
Tissue Specificity:
Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.
Post-translational modifications:
Cleavage by granzyme B and autocatalytic activity generate the two active subunits.
Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE:
Defects in CASP10 are the cause of autoimmune lymphoproliferative syndrome type 2A (ALPS2A) [MIM:603909]. ALPS2 is characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects.
Defects in CASP10 are a cause of familial non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.
Similarity:
Belongs to the peptidase C14A family.
Contains 2 DED (death effector) domains.
Database links:
Entrez Gene: 843 Human
Omim: 601762 Human
SwissProt: Q92851 Human
Unigene: 5353 Human
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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