CASP3

Caspase-3 • UniProt accession P42574

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)

Source: UniProt

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce

Source: UniProt
Cytoplasm
Source: UniProt

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

Source: UniProt
  • Activation of caspases through apoptosome-mediated cleavage
  • SMAC (DIABLO) binds to IAPs
  • SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes
  • Apoptotic cleavage of cellular proteins
  • SMAC, XIAP-regulated apoptotic response
  • Apoptosis induced DNA fragmentation
  • Degradation of the extracellular matrix
  • Signaling by Hippo
  • NADE modulates death signalling
  • Stimulation of the cell death response by PAK-2p34
  • Caspase-mediated cleavage of cytoskeletal proteins
  • Apoptotic cleavage of cell adhesion proteins
  • Caspase activation via Dependence Receptors in the absence of ligand
  • Other interleukin signaling
  • Pyroptosis
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CASP3, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 18

NCT ID Condition Brief Title Phase Status
NCT04548674 Pulp Inflammation Analysis of the Influence of Desensitizing Treatments on the Pulp Inflammatory Response in Bleached Teeth NA COMPLETED
NCT01664000 Solid Tumors A Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin in Patients With Advanced Solid Tumors PHASE1 COMPLETED
NCT06850831 STEMI - ST Elevation Myocardial Infarction (MI), Primary PCI - STEMI Effect of Intracoronary N-Acetylcysteine in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention PHASE2 COMPLETED
NCT05175638 COVID-19 Pandemic Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers. N/A UNKNOWN
NCT04984031 Molar-incisor Pattern Grade C Periodontitis ( Localized Aggressive Periodontitis), Generalized Grade C Periodontitis (Generalized Aggressive Periodontitis) Apoptosis Markers in Aggressive Periodontitis N/A COMPLETED
NCT06615674 Acute Myocardial Infarction (AMI), STEMI - ST Elevation Myocardial Infarction (MI), NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI) Effect of Dapagliflozin Administration on the Apoptosis Levels of Patients With Acute Myocardial Infarction PHASE4 COMPLETED
NCT05822908 Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 3, Huntington Disease A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD PHASE1, PHASE2 RECRUITING
NCT05456776 Inflammatory Bowel Diseases Azathioprine Linked With Impaired Intestinal Epithelial Postoperative Regeneration in Crohn's Disease N/A COMPLETED
NCT03487367 Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia 3 Clinical Trial Readiness for SCA1 and SCA3 N/A UNKNOWN
NCT06195371 Breast Cancer Impact of CASP3 Gene in Chemoresistance N/A NOT_YET_RECRUITING