CASP3

GeneName

CASP3

Summary

CASP3, also known as caspase-3 or cleaved caspase-3, is a 32kDa cysteine protease that plays a pivotal role in the execution phase of apoptosis. It is primarily expressed in the cytoplasm and nucleus, and is involved in various cellular processes including the apoptotic signaling pathway and DNA damage response. CASP3 is activated in response to pro-apoptotic signals and cleaves specific substrates leading to cellular disassembly. It is also implicated in non-apoptotic functions such as synaptic plasticity and neurodevelopment, particularly in the hippocampus and during heart development.

Importance

CASP3 is relevant to: - Understanding apoptosis and its regulation, which has implications in cancer research and therapy - Neurodegenerative diseases, where dysregulation of apoptosis contributes to neuronal loss - Immune responses, as it plays a role in the negative regulation of T and B cell proliferation - Cardiovascular health, given its involvement in heart development and response to stressors - Drug discovery, particularly in the context of targeting apoptotic pathways for therapeutic intervention

Top Products

For researchers investigating CASP3, we recommend two excellent primary antibodies that cater to different needs. The first is the highly regarded polyclonal antibody, Anti-Cleaved Caspase-3 antibody (ab2302), which has garnered an impressive 1580 citations, underscoring its reliability in Western blotting (WB). Additionally, we offer the recombinant monoclonal antibody, Anti-Cleaved Caspase-3 antibody [E83-77] (ab32042). This antibody has been validated in knockout models and is suitable for both WB and immunocytochemistry (ICC), making it a versatile option for those requiring consistent performance across applications. With 919 citations, it is well-established in the research community, providing researchers with confidence in their CASP3 studies. The Anti-Caspase-3 antibody ELISA Kit (ab13585), supported by 118 citations, is an excellent option for researchers looking to accurately measure Caspase-3 levels in their samples.

Abcam Product Citation Summary

The data indicates a significant focus on the role of CASP3 in various forms of apoptosis across multiple species, particularly in human cancer cell lines and rat models. The studies highlight its involvement in processes such as chemoresistance, neuroprotection, and the effects of various treatments on cell viability. The use of different applications, primarily Western blotting, underscores the importance of CASP3 as a marker for apoptotic activity in both normal and pathological conditions.

Abcam Product Citation Table

Function

Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:7596430). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:10497198, PubMed:16374543, PubMed:7596430, PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) (PubMed:7596430). Cleaves and inactivates interleukin-18 (IL18) (PubMed:37993714, PubMed:9334240). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves DSG2 in response to apoptosis resulting in a loss of full length DSG2 at desmosome cell junctions and subsequent loss of cell-cell adhesion (PubMed:17559062). Also cleaves JUP in response to apoptosis (PubMed:17559062). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35338844, PubMed:35446120). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106).

Post-translational modifications

Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits (PubMed:35338844, PubMed:35446120, PubMed:7596430, PubMed:8755496). Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease (PubMed:7596430, PubMed:8755496). Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa (PubMed:7596430, PubMed:8755496).

S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol.

Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.

(Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP3 processing, preventing CASP3 activation and ability to recognize and cleave substrates.

Sequence Similarities

Belongs to the peptidase C14A family.

Tissue Specificity

Highly expressed in lung, spleen, heart, liver and kidney. Moderate levels in brain and skeletal muscle, and low in testis. Also found in many cell lines, highest expression in cells of the immune system.

Cellular localization

• Cytoplasm

Alternative names

CPP32, CASP3, Caspase-3, CASP-3, Apopain, Cysteine protease CPP32, Protein Yama, SREBP cleavage activity 1, CPP-32, SCA-1

Database links

swissprot:P42574 entrezGene:836 omim:600636

Other research areas

• Immunology & Infectious Disease