Human Caspase-1: Difference between revisions
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Caspases (cysteine-aspartic proteases) are proteolytic enzymes that play essential roles in [http://en.wikipedia.org/wiki/Apoptosis apoptosis], development, inflammation, and the immune system. As the name suggests, caspases cleave proteins on the C-side of aspartic acid residues. As of now, around 15 caspases have been identified in two categories, inflammatory (in which caspase-1 is classified) and apoptotic. Apoptotic caspases are further divided into initiator (apical) caspases and effector (executioner) caspases. Initiator caspases cleave and activate effector caspases, which in turn start apoptosis by cleaving other proteins in a cascade reaction. Faulty or premature apoptosis is a main component of autoimmune diseases, leading to research into caspase inhibitors to treat diseases like Alzheimer's. Inflammatory caspases on the other hand usually work by proteolytically activating cytokines, leading to a different kind of cell mediated death called [http://en.wikipedia.org/wiki/Pyroptosis pyroptosis]. | Caspases (cysteine-aspartic proteases) are proteolytic enzymes that play essential roles in [http://en.wikipedia.org/wiki/Apoptosis apoptosis], development, inflammation, and the immune system. As the name suggests, caspases cleave proteins on the C-side of aspartic acid residues. As of now, around 15 caspases have been identified in two categories, inflammatory (in which caspase-1 is classified) and apoptotic. Apoptotic caspases are further divided into initiator (apical) caspases and effector (executioner) caspases. Initiator caspases cleave and activate effector caspases, which in turn start apoptosis by cleaving other proteins in a cascade reaction. Faulty or premature apoptosis is a main component of autoimmune diseases, leading to research into caspase inhibitors to treat diseases like Alzheimer's. Inflammatory caspases on the other hand usually work by proteolytically activating cytokines, leading to a different kind of cell mediated death called [http://en.wikipedia.org/wiki/Pyroptosis pyroptosis]. | ||
[[image:Caspase-1_Zymogen.jpg|thumb|right|200px|'''Human Caspase-1 Zymogen''']] | |||
==Activation and Regulation== | ==Activation and Regulation== | ||
<scene name='Human_Caspase-1/Caspase-1/1'>Caspase-1</scene> begins as a [http://en.wikipedia.org/wiki/Zymogen zymogen], with its two subunits and a CARD prodomain all in one peptide sequence. Activation is thought to be initiated by removal of the [http://en.wikipedia.org/wiki/CARD_domain CARD domain] and dimerization. Bonds between subunits can be cleaved, leading to the maturation of the enzyme, but this does not necessarily convey greater activity. ASC and Ipaf have been identified as possible regulators of caspase-1 in a structure called the inflammasome. ASC leads to ATP-driven activation of caspase-1, while Ipaf connects signals triggered by intracellular pathogens.<ref name=Mariathasan>PMID:15190255</ref> Both of these activators are essential for caspase-1 driven cell death, showing a link between inflammation and apoptosis. Adaptors in the inflammasome react to extracellular and endogenous danger signals, usually flaggelin, to activate caspase-1 and begin the inflammatory response.<ref name=Franchi>PMID:19221555</ref> | <scene name='Human_Caspase-1/Caspase-1/1'>Caspase-1</scene> begins as a [http://en.wikipedia.org/wiki/Zymogen zymogen], with its two subunits and a CARD prodomain all in one peptide sequence. Activation is thought to be initiated by removal of the [http://en.wikipedia.org/wiki/CARD_domain CARD domain] and dimerization. Bonds between subunits can be cleaved, leading to the maturation of the enzyme, but this does not necessarily convey greater activity. ASC and Ipaf have been identified as possible regulators of caspase-1 in a structure called the inflammasome. ASC leads to ATP-driven activation of caspase-1, while Ipaf connects signals triggered by intracellular pathogens.<ref name=Mariathasan>PMID:15190255</ref> Both of these activators are essential for caspase-1 driven cell death, showing a link between inflammation and apoptosis. Adaptors in the inflammasome react to extracellular and endogenous danger signals, usually flaggelin, to activate caspase-1 and begin the inflammatory response.<ref name=Franchi>PMID:19221555</ref> | ||
==Structure== | ==Structure== | ||