CASP6

Description

The CASP6 (caspase 6) is a protein-coding gene located on chromosome 4.

Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease.

== Function == This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene results in two transcript variants that encode different isoforms.

Caspase-6 (CASP6) is a cysteine protease involved in various cellular processes, including programmed cell death (apoptosis), axonal degeneration, development, and innate immunity. It acts as a non-canonical executioner caspase during apoptosis, localizing to the nucleus and cleaving nuclear structural proteins NUMA1 and lamin A/LMNA, leading to nuclear shrinkage and fragmentation. Lamin-A/LMNA cleavage is essential for chromatin condensation and nuclear disassembly during apoptosis. Caspase-6 also plays a role in regulating liver damage by promoting hepatocyte apoptosis. In the absence of phosphorylation by AMP-activated protein kinase (AMPK), Caspase-6 cleaves BID, triggering cytochrome c release and contributing to nonalcoholic steatohepatitis. Furthermore, Caspase-6 cleaves various transcription factors, including NF-kappa-B and cAMP response element-binding protein/CREBBP, and phospholipid scramblase proteins XKR4 and XKR9. Beyond apoptosis, Caspase-6 participates in other forms of programmed cell death. It plays a crucial role in defense against viruses by acting as a central mediator of ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis), independent of its cysteine protease activity. PANoptosis is a unique inflammatory programmed cell death that involves the activation of inflammasome/pyroptosis, apoptosis, and necroptosis machinery. Caspase-6 interacts with RIPK3, enhancing the interaction between RIPK3 and ZBP1, leading to ZBP1-mediated inflammasome activation and cell death. Additionally, Caspase-6 is essential for axon degeneration during axon pruning, a process that remodels axons during neurogenesis, and it regulates B-cell programs during early development and after antigen stimulation.

CASP6 is also known as CSP-6, MCH2, caspase-6.

Associated Diseases

WES Whole Exome Sequencing