WordNet

any of a group of proteases that mediate apoptosis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/05 05:28:42」(JST)

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Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis, pyroptosis and necroptosis) and inflammation. They are named Caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only at the C-terminal of an aspartic acid amino acid. As of 2009, there are 11-12 confirmed Caspases in humans (since caspase-12 is a pseudogene in some individuals; Nature Medicine 11, 725 - 730 (2005)) and 10 in mice, carrying out a variety of cellular functions.

The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of Caspases ensure that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect to surrounding tissues.^[2]

Caspases have other identified roles in programmed cell death such as Pyroptosis and Necroptosis. These forms of cell death are important for protecting an organism from stress signals and pathogenic attack. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. These are signalling molecules that allow recruitment of immune cells to an infected cell or tissue. There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing^[3]

Caspase deficiency has been identified as a cause of tumour development. Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restrains of cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormal growing cells.^[4] On the contrary, over activation of some caspases such as caspase-3 can lead to excessive programmed cell death. This is seen in several neurodegenerative diseases where neural cells are lost, such as Alzheimers disease.^[4] Caspases involved with processing inflammatory signals are also implicated in disease. Insufficient activation of these caspases can increase the organisms susceptibility to infection as an appropriate immune response may not be activated.^[4] The integral role caspases play in cell death and disease has led to research for using caspases as a drug target. For example, inflammatory caspase-1 has been implicated in causing autoimmune diseases; drugs blocking the activation of Caspase-1 have been used to improve the health of patients. Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours.^[5]

Functional classification of caspases

Most caspases play a role in programmed cell death. These are summarised in the table below. The enzymes are sub classified into three types: Initiator, Executioner and Inflammatory.^[6]

Programmed Cell Death	Type of Caspase	Enzyme	Organism
Apoptosis	Initiator	Caspase 2	human and mouse
		Caspase 8	human and mouse
		Caspase 9	human and mouse
		Caspase 10	human only (Science. 2006 Jun 30;312(5782):1874. Caspase-10 in mouse or not? Jänicke RU, Sohn D, Totzke G, Schulze-Osthoff K.)
	Executioner	Caspase 3	human and mouse
		Caspase 6	human and mouse
		Caspase 7	human and mouse
Pyroptosis	Inflammatory	Caspase 1	human and mouse
		Caspase 4	human
		Caspase 5	human
		Caspase 11	mouse
		Caspase 12	mouse and some humans
Other roles	Other	Caspase 14	human and mouse

Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis. Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation.^[7]

Activation of caspases

Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus. This post-translational level of control allows rapid and tight regulation of the enzyme.

Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. The large and small subunit associate with each other to form an active heterodimer caspase. The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer.^[8]

Dimerisation

Dimerisation is facilitated by a particular domain called the pro-domain. This domain is larger in Initiator and Inflammatory Caspases, consisting of Caspase Recruitment Domains (CARD) and Death Effector Domains (DED), used to mediate protein-protein interactions between caspases. Adaptor proteins are used by some caspases, to assist this interaction.

Multiprotein complexes often form during pro-caspase activation.^[8] Some activating multiprotein complexes includes:

Apoptosome and Death Induced Signalling Complex (DISC) during apoptosis
Inflammasome during pyroptosis

Cleavage

Once appropriately dimerised, the Caspases cleaves at inter domain linker regions, forming a large and small subunit. This cleavage allows the active-site loops to take up a conformation favourable for enzymatic activity.^[9]

Cleavage of Initiator and Executioner caspases occur by different methods outlined in the table below.

Initiator caspases auto-proteolytically cleave whereas Executioner caspases are cleaved by initiator caspases. This hierarchy allows an amplifying chain reaction or cascade for degrading cellular components, during controlled cell death.

Initiator Caspase Caspase-8	Inititator Caspases have a prodomain that allows recruitment and dimerisation. Adaptor proteins such as FADD represented by the grey DED domains, can assist this interaction. Both pro-caspase moleucules undergo cleavage by autocatalysis at the regions marked in red. This leads to removal of the prodomain and cleavage of the linker region between the large and small subunit. A heterotetramer can therefore form.	PDB image of caspase 8 (3KJQ) in 'biological assembly'. Two shades of blue used to represent two small sunits, one from each Caspase-8, while two shades of purple represent two large subunits, one from each Caspase-8.
Executioner Caspase Caspase-3	Executioner caspase can constitutively exist as homodimers. The red cuts represent regions where initiator caspases can cleave the executioner caspases. The resulting small and large subunit of each Caspase-3 will associate, resulting in a heterotetramer.^[10]	PDB image of Caspase 3 (4QTX) in 'biological assembly'. Two shades of blue used to represent two small sunits, while two shades of purple represent two large subunits

Some roles of caspases

Apoptosis

Apoptosis is a form of programmed cell death where the cell undergoes morphological changes, to minimize its effect on surrounding cells to avoid inducing an immune response. The cell shrinks and condenses - the cytoskeleton will collapse, the nuclear envelope disassembles and the DNA fragments up. This results in the cell forming self-enclosed bodies called 'blebs', to avoid release of cellular components into the extracellular medium. Additionally, the cell membrane phospholipid content is altered, which makes the dying cell more susceptible to phagocytic attack and removal.^[11]

Apoptopic caspases are subcategorised as:

Initiator Caspases (Caspase 2, Caspase 8, Caspase-9, Caspase 10)
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7)

Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. Executioner caspases degrade over 600 cellular components^[12] in order to induce the morphological changes for apoptosis.

Examples of caspase cascade during apoptosis:

Intrinsic apoptopic pathway: During times of cellular stress, mitochondrial cytochrome c is released into the cytosol. This molecule binds an adaptor protein (APAF-1), which recruits initiator Caspase-9 (via CARD-CARD interactions). This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator caspases such as Caspase 9 will cleave and activate other executioner caspases. This leads to degradation of cellular components for apoptosis.
Extrinsic apoptopic pathway: The caspase cascade is also activated by extracellular ligands, via cell surface Death Receptors. This is done by the formation of a multiprotein Death Inducing Signalling Complex (DISC) that recruits and activates a pro-caspase. For example, the Fas Ligand binds the FasR receptor at the receptor's extracellular surface; this activates the death domains at the cytoplasmic tail of the receptor. The adaptor protein FADD will recruit (by a Death domain-Death domain interaction). The other end of the adaptor contains a DED domain for pro-caspase recruitment. This FasR, FADD and pro-Caspase 8 form the Death Inducing Signalling Complex (DISC) where Caspase-8 is activated. This could lead to either downstream activation of the intrinsic pathway by inducing mitochondrial stress, or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in the adjacent diagram.^[13]

Pyroptosis

Pyroptosis is a form of programmed cell death that inherently induces an immune response. It is morphologically distinct from other types of cell death – cells swell up, rupture and release pro-inflammatory cellular contents. This is done in response to a range of stimuli including microbial infections as well as heart attacks (myocardial infarctions).^[14] Caspase-1, Caspase-4 and Caspase-5 in humans whereas Caspase-1 and Caspase-11 in mice play important roles in inducing cell death by Pyroptosis. This could lead to limiting the life and proliferation time of intracellular and extracellular pathogens.

Pyroptosis by caspase-1

Caspase-1 activation is mediated by a repertoire of proteins, allowing detection of a range of pathogenic ligands. Some mediators of Caspase-1activation are: NOD-like Leucine Rich Repeats (NLRs), AIM2-Like Receptors (ALRs), Pyrin and IFI16.^[15]

These proteins allow caspase-1 activation by forming a multiprotein activating complex called Inflammasomes. For example, a NOD Like Leucine Rich Repeat NLRP3 will sense an efflux of potassium ions from the cell. This cellular ion imbalance leads to oligomerisation of NLRP3 molecules to form a multiprotein complex called the NLRP3 Inflammasome. The pro-caspase-1 is brought into close proximity with other pro-caspase molecule in order to dimerise and undergo auto-proteolytic cleavage.^[15]

Some pathogenic signals that lead to Pyroptosis by Caspase-1 are listed below:

DNA in the host cytosol binds to AIM2-Like Receptors inducing Pyroptosis
Type III secretion system apparatus from bacteria bind NOD Like Leucine Rich Repeats receptors called NAIP’s (1 in humans and 4 in mice)

Pyroptosis by Caspase -4 and Caspase-5 in humans and Caspase-11 in mice

These caspases have the ability to induce direct pyroptosis when LPS molecules (found in the cell wall of gram negative bacteria) are found in the cytoplasm of the host cell. For example, Caspase 4 acts as a receptor and is proteolytically activated, without the need of an inflammasome complex or Caspase-1 activation.^[15]

A crucial downstream substrate for pyroptopic caspases is Gasdermin D (GSDMD)^[16]

Role in inflammation

Inflammation is a protective attempt by an organism to restore a homeostatic state, following disruption from harmful stimulus, such as tissue damage or bacterial infection.^[12]

Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.^[6]

Caspase-1 is key in activating pro-inflammatory cytokines; these act as signals to immune cells and make the environment favourable for immune cell recruitment to the site of damage. Caspase-1 therefore plays has a fundamental role in the innate immune system. The enzyme is responsible for processing cytokines such as pro-ILβ and pro-IL18, as well as secreting them.^[15]
Caspase-4 and -5 in humans, and Caspase-11 in mice have a unique role as a receptor, whereby it binds to LPS, a molecule abundant in gram negative bacteria. This can lead to the processing and secretion of IL-1β and IL-18 cytokines by activating Caspase-1; this downstream effect is the same as described above. It also leads to the secretion of another inflammatory cytokine that is not processed. This is called pro-IL1α.^[15] There is also evidence of an inflammatory caspase, caspase-11 aiding cytokine secretion; this is done by inactivating a membrane channel that blocks IL-1β secretion^[15]
Caspases can also induce an inflammatory response on a transcriptional level. There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in transcribing inflammatory cytokines such as IFNs, TNF, IL-6 and IL-8. For example, Caspase-1 activates Caspase-7, which in turn cleaves the poly (ADP) ribose – this activates transcription of NF-κB controlled genes.^[12]

Discovery of caspases

H. Robert Horvitz initially established the importance of caspases in apoptosis and found that the ced-3 gene is required for the cell death that took place during the development of the nematode C. elegans. Horvitz and his colleague Junying Yuan found in 1993 that the protein encoded by the ced-3 gene is cysteine protease with similar properties to the mammalian interleukin-1-beta converting enzyme (ICE) (now known as caspase 1). At the time, ICE was the only known caspase.^[17] Other mammalian caspases were subsequently identified, in addition to caspases in organisms such as fruit fly Drosophila melanogaster.

Researchers decided upon the nomenclature of the caspase in 1996. In many instances, a particular caspase had been identified simultaneously by more than one laboratory, who would each give the protein a different name. For example, caspase 3 was variously known as CPP32, apopain and Yama. Caspases, therefore, were numbered in the order in which they were identified.^[18] ICE was, therefore, renamed as caspase 1. ICE was the first mammalian caspase to be characterised because of its similarity to the nematode death gene ced-3, but it appears that the principal role of this enzyme is to mediate inflammation rather than cell death.

References

^ Wilson KP, Black JA, Thomson JA, et al. (July 1994). "Structure and mechanism of interleukin-1 beta converting enzyme". Nature. 370 (6487): 270–5. doi:10.1038/370270a0. PMID 8035875.
^ Rathore, S.; Datta, G.; Kaur, I.; Malhotra, P.; Mohmmed, A. (2015-07-02). "Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite". Cell Death & Disease. 6 (7): e1803. doi:10.1038/cddis.2015.142. PMC 4650714. PMID 26136076.
^ Shalini, S.; Dorstyn, L.; Dawar, S.; Kumar, S. (2015-04-01). "Old, new and emerging functions of caspases". Cell Death & Differentiation. 22 (4): 526–539. doi:10.1038/cdd.2014.216. ISSN 1350-9047. PMC 4356345. PMID 25526085.
^ ^a ^b ^c Goodsell, David S. (2000-10-01). "The Molecular Perspective: Caspases". The Oncologist. 5 (5): 435–436. doi:10.1634/theoncologist.5-5-435. ISSN 1083-7159. PMID 11040280.
^ McIlwain, David R.; Berger, Thorsten; Mak, Tak W. (2013-04-01). "Caspase Functions in Cell Death and Disease". Cold Spring Harbor Perspectives in Biology. 5 (4): a008656. doi:10.1101/cshperspect.a008656. ISSN 1943-0264. PMC 3683896. PMID 23545416.
^ ^a ^b Galluzzi, Lorenzo; López-Soto, Alejandro; Kumar, Sharad; Kroemer, Guido (2016-02-16). "Caspases Connect Cell-Death Signaling to Organismal Homeostasis". Immunity. 44 (2): 221–231. doi:10.1016/j.immuni.2016.01.020. ISSN 1074-7613. PMID 26885855.
^ Denecker, Geertrui; Ovaere, Petra; Vandenabeele, Peter; Declercq, Wim (2008-02-11). "Caspase-14 reveals its secrets". The Journal of Cell Biology. 180 (3): 451–458. doi:10.1083/jcb.200709098. ISSN 0021-9525. PMC 2234247. PMID 18250198.
^ ^a ^b Shi, Yigong (2004-06-25). "Caspase Activation". Cell. 117 (7): 855–858. doi:10.1016/j.cell.2004.06.007. ISSN 0092-8674. PMID 15210107.
^ Riedl, Stefan J.; Shi, Yigong (Nov 2004). "Molecular mechanisms of caspase regulation during apoptosis". Nature Reviews Molecular Cell Biology. 5 (11): 897–907. doi:10.1038/nrm1496. PMID 15520809.
^ Lavrik, I.; Krueger, A.; Schmitz, I.; Baumann, S.; Weyd, H.; Krammer, P. H.; Kirchhoff, S. (2003-01-01). "The active caspase-8 heterotetramer is formed at the CD95 DISC". Cell Death & Differentiation. 10 (1): 144–145. doi:10.1038/sj.cdd.4401156. ISSN 1350-9047.
^ Elmore, Susan (2007-06-01). "Apoptosis: A Review of Programmed Cell Death". Toxicologic Pathology. 35 (4): 495–516. doi:10.1080/01926230701320337. ISSN 0192-6233. PMC 2117903. PMID 17562483.
^ ^a ^b ^c Sollberger, Gabriel; Strittmatter, Gerhard E.; Garstkiewicz, Martha; Sand, Jennifer; Beer, Hans-Dietmar (2014-02-01). "Caspase-1: The inflammasome and beyond". Innate Immunity. 20 (2): 115–125. doi:10.1177/1753425913484374. ISSN 1753-4259. PMID 23676582.
^ Creagh, Emma M. (December 2014). "Caspase crosstalk: integration of apoptotic and innate immune signalling pathways". Trends in Immunology. 35 (12): 631–640. doi:10.1016/j.it.2014.10.004. PMID 25457353.
^ Bergsbaken, Tessa; Fink, Susan L.; Cookson, Brad T. "Pyroptosis: host cell death and inflammation". Nature Reviews Microbiology. 7 (2): 99–109. doi:10.1038/nrmicro2070. PMC 2910423. PMID 19148178.
^ ^a ^b ^c ^d ^e ^f Eldridge, Matthew JG; Shenoy, Avinash R. "Antimicrobial inflammasomes: unified signalling against diverse bacterial pathogens". Current Opinion in Microbiology. 23: 32–41. doi:10.1016/j.mib.2014.10.008.
^ He, Wan-ting; Wan, Haoqiang; Hu, Lichen; Chen, Pengda; Wang, Xin; Huang, Zhe; Yang, Zhang-Hua; Zhong, Chuan-Qi; Han, Jiahuai (2015-12-01). "Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion". Cell Research. 25 (12): 1285–1298. doi:10.1038/cr.2015.139. ISSN 1001-0602. PMC 4670995. PMID 26611636.
^ Yuan, J; et al. (1993). "The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme". Cell. 75 (4): 641–652. doi:10.1016/0092-8674(93)90485-9. PMID 8242740.
^ Alnemri ES, Emad S; et al. (1996). "Human ICE/CED-3 Protease Nomenclature". Cell. 87 (2): 171. doi:10.1016/S0092-8674(00)81334-3. PMID 8861900. Retrieved 6 March 2011.

External links

Eukaryotic Linear Motif resource motif class CLV_C14_Caspase3-7
Apoptosis Video Demonstrates a model of a caspase cascade as it occurs in vivo.
The Mechanisms of Apoptosis Kimball's Biology Pages. Simple explanation of the mechanisms of apoptosis triggered by internal signals (bcl-2), along the caspase-9, caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. Accessed 25 March 2007.
Apoptosis & Caspase 7, PMAP-animation
Caspases at the US National Library of Medicine Medical Subject Headings (MeSH)
Tumors Beware (from Beaker Blog)

UpToDate Contents

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1. 複合免疫不全 combined immunodeficiencies
2. アポトーシスと自己免疫疾患 apoptosis and autoimmune disease
3. 混合性結合組織病における抗U1-RNP抗体 anti u1 rnp antibodies in mixed connective tissue disease
4. 自己免疫性リンパ増殖症候群(ALPS)：疫学および病因 autoimmune lymphoproliferative syndrome alps epidemiology and pathogenesis
5. 肝線維症の新しい治療法 emerging therapies for hepatic fibrosis

English Journal

Regulation of hippocampal Fas receptor and death-inducing signaling complex after kainic acid treatment in mice.

Keller B1, García-Sevilla JA2.
Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2015 Dec 3;63:54-62. doi: 10.1016/j.pnpbp.2015.04.009. Epub 2015 Jun 2.
Kainic acid (KA)-induced brain neuronal cell death (especially in the hippocampus) was shown to be mainly mediated by the intrinsic (mitochondrial) apoptotic pathway. This study investigated the regulation of the extrinsic apoptotic pathway mediated by Fas ligand/Fas receptor and components of the i
PMID 26044520

NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio).

SanJuan-Reyes N1, Gómez-Oliván LM2, Galar-Martínez M3, García-Medina S3, Islas-Flores H1, González-González ED1, Cardoso-Vera JD1, Jiménez-Vargas JM4.
The Science of the total environment.Sci Total Environ.2015 Oct 15;530-531:1-10. doi: 10.1016/j.scitotenv.2015.05.088. Epub 2015 May 27.
The pharmaceutical industry generates wastewater discharges of varying characteristics and contaminant concentrations depending on the nature of the production process. The main chemicals present in these effluents are solvents, detergents, disinfectants - such as sodium hypochlorite (NaClO) - and p
PMID 26026403

Guggulsterone and bexarotene induce secretion of exosome-associated breast cancer resistance protein and reduce doxorubicin resistance in MDA-MB-231 cells.

Kong JN1, He Q1, Wang G1, Dasgupta S1,2, Dinkins MB1, Zhu G1, Kim A1, Spassieva S3, Bieberich E1.
International journal of cancer. Journal international du cancer.Int J Cancer.2015 Oct 1;137(7):1610-20. doi: 10.1002/ijc.29542. Epub 2015 Apr 27.
Many breast cancer cells acquire multidrug resistance (MDR) mediated by ABC transporters such as breast cancer resistance protein (BCRP/ABCG2). Here we show that incubation of human breast cancer MDA-MB-231 cells with farnesoid X receptor antagonist guggulsterone (gug) and retinoid X receptor agonis
PMID 25833198

Japanese Journal

Carboxylic Derivatives of Vitamin K2 Inhibit Hepatocellular Carcinoma Cell Growth through Caspase/Transglutaminase-Related Signaling Pathways

QIN Xian-Yang,FUJII Shinya,SHIMIZU Akitaka [他]
Journal of nutritional science and vitaminology 61(4), 285-290, 2015-08
NAID 40020570335

Apoptosis induction by aluminum phthalocyanine tetrasulfonate-based sonodynamic therapy in HL-60 cells

Iwase Yumiko,Yumita Nagahiko,Nishi Koji,Kuwahara Hiroyuki,Fukai Toshio,Ikeda Toshihiko,Chen Fu-shih,Momose Yasunori,Umemura Shin-ichiro
Jpn. J. Appl. Phys. 54(7S1), 07HD05, 2015-06-08
… Apoptosis was analyzed by cell morphology, DNA fragmentation, and caspase-3 activity. … Furthermore, DNA ladder formation, caspase-3 activation and enhanced nitroxide generation were observed in cells treated with ultrasound and AlPcTS. … Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. …
NAID 150000110984

プロテアソーム阻害剤およびIMiDsの作用機序研究の進展 (特集多発性骨髄腫をめぐる最近の進歩と話題)

菊池次郎,古川雄祐
血液内科 = Hematology 70(6), 690-697, 2015-06
NAID 40020529726

Related Pictures

★リンクテーブル★

リンク元	「カスパーゼ」「カスペース」
拡張検索	「caspase 1」「caspase inhibitor」「caspase recruitment domain」

「カスパーゼ」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Caspase domain
	Structure of interleukin-1 beta-converting enzyme.
Identifiers
Symbol	Peptidase_C14
Pfam	PF00656
Pfam clan	CL0093
InterPro	IPR002398
PROSITE	PS50208
MEROPS	C14
SCOP	1ice
SUPERFAMILY	1ice
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

英: caspase
同: ICEファミリープロテアーゼ ICE family protease

ヒトICEプロテアーゼスーパーファミリー

Family	Caspase	Other Name	Recognition	Target (Truncation site)
caspase-1	caspase-1	ICE	WEHD	pro IL-1β (FEAD/G, YVHD/A), procaspase-3, procaspase-4
	caspase-4	ICErel-II, TX, ICH-2
	caspase-5	ICErel-III, TY
caspase-2	caspase-2	ICH-1	DEHD	PARP (DEVD/G)
caspase-2	caspase-9	ICE-LAP6, Mch6	LEHD	PARP, procaspase-3
caspase-3	caspase-3	CPP32, Yama	DEVD	PARP, SREBP (DEPD/S), U1snRNP (DGPD/G), lamin B, D4-GDI (DELD/S), DNA-PK (DEVD/N), DFF (DETD/S, DAVD/T), actin (ELPD/G) ?, PKCδ (DMQD/N) ?]]
	caspase-7	Mch3, ICE-LAP3, CMH-1	DEVD	PARP, procaspase-6
	caspase-6	Mch2	VEHD	lamin A (VEID/N)]]
	caspase-8	FLICE, MACH, Mch5	LETD	procaspase-3, Bid
	caspase-10	Mch4	LEXD
	caspase-11	Ich3

「カスペース」

　　[★]

英: caspase
関: カスパーゼ

「caspase 1」

　　[★]

カスパーゼ1

関: IL-1 beta-converting enzyme、interleukin-1beta converting enzyme

「caspase inhibitor」

　　[★]

カスパーゼ阻害剤、カスパーゼ阻害薬

「caspase recruitment domain」

　　[★]

カスパーゼ動員ドメイン

関: CARD

[pmid8035875-1] Wilson KP, Black JA, Thomson JA, et al. (July 1994). "Structure and mechanism of interleukin-1 beta converting enzyme". Nature. 370 (6487): 270–5. doi:10.1038/370270a0. PMID 8035875.

[2] Rathore, S.; Datta, G.; Kaur, I.; Malhotra, P.; Mohmmed, A. (2015-07-02). "Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite". Cell Death & Disease. 6 (7): e1803. doi:10.1038/cddis.2015.142. PMC 4650714. PMID 26136076.

[3] Shalini, S.; Dorstyn, L.; Dawar, S.; Kumar, S. (2015-04-01). "Old, new and emerging functions of caspases". Cell Death & Differentiation. 22 (4): 526–539. doi:10.1038/cdd.2014.216. ISSN 1350-9047. PMC 4356345. PMID 25526085.

[:0-4] Goodsell, David S. (2000-10-01). "The Molecular Perspective: Caspases". The Oncologist. 5 (5): 435–436. doi:10.1634/theoncologist.5-5-435. ISSN 1083-7159. PMID 11040280.

[5] McIlwain, David R.; Berger, Thorsten; Mak, Tak W. (2013-04-01). "Caspase Functions in Cell Death and Disease". Cold Spring Harbor Perspectives in Biology. 5 (4): a008656. doi:10.1101/cshperspect.a008656. ISSN 1943-0264. PMC 3683896. PMID 23545416.

[:5-6] Galluzzi, Lorenzo; López-Soto, Alejandro; Kumar, Sharad; Kroemer, Guido (2016-02-16). "Caspases Connect Cell-Death Signaling to Organismal Homeostasis". Immunity. 44 (2): 221–231. doi:10.1016/j.immuni.2016.01.020. ISSN 1074-7613. PMID 26885855.

[:4-7] Denecker, Geertrui; Ovaere, Petra; Vandenabeele, Peter; Declercq, Wim (2008-02-11). "Caspase-14 reveals its secrets". The Journal of Cell Biology. 180 (3): 451–458. doi:10.1083/jcb.200709098. ISSN 0021-9525. PMC 2234247. PMID 18250198.

[:3-8] Shi, Yigong (2004-06-25). "Caspase Activation". Cell. 117 (7): 855–858. doi:10.1016/j.cell.2004.06.007. ISSN 0092-8674. PMID 15210107.

[9] Riedl, Stefan J.; Shi, Yigong (Nov 2004). "Molecular mechanisms of caspase regulation during apoptosis". Nature Reviews Molecular Cell Biology. 5 (11): 897–907. doi:10.1038/nrm1496. PMID 15520809.

[10] Lavrik, I.; Krueger, A.; Schmitz, I.; Baumann, S.; Weyd, H.; Krammer, P. H.; Kirchhoff, S. (2003-01-01). "The active caspase-8 heterotetramer is formed at the CD95 DISC". Cell Death & Differentiation. 10 (1): 144–145. doi:10.1038/sj.cdd.4401156. ISSN 1350-9047.

[11] Elmore, Susan (2007-06-01). "Apoptosis: A Review of Programmed Cell Death". Toxicologic Pathology. 35 (4): 495–516. doi:10.1080/01926230701320337. ISSN 0192-6233. PMC 2117903. PMID 17562483.

[:1-12] Sollberger, Gabriel; Strittmatter, Gerhard E.; Garstkiewicz, Martha; Sand, Jennifer; Beer, Hans-Dietmar (2014-02-01). "Caspase-1: The inflammasome and beyond". Innate Immunity. 20 (2): 115–125. doi:10.1177/1753425913484374. ISSN 1753-4259. PMID 23676582.

[13] Creagh, Emma M. (December 2014). "Caspase crosstalk: integration of apoptotic and innate immune signalling pathways". Trends in Immunology. 35 (12): 631–640. doi:10.1016/j.it.2014.10.004. PMID 25457353.

[14] Bergsbaken, Tessa; Fink, Susan L.; Cookson, Brad T. "Pyroptosis: host cell death and inflammation". Nature Reviews Microbiology. 7 (2): 99–109. doi:10.1038/nrmicro2070. PMC 2910423. PMID 19148178.

[:2-15] ^ ^a ^b ^c ^d ^e ^f Eldridge, Matthew JG; Shenoy, Avinash R. "Antimicrobial inflammasomes: unified signalling against diverse bacterial pathogens". Current Opinion in Microbiology. 23: 32–41. doi:10.1016/j.mib.2014.10.008.

[16] He, Wan-ting; Wan, Haoqiang; Hu, Lichen; Chen, Pengda; Wang, Xin; Huang, Zhe; Yang, Zhang-Hua; Zhong, Chuan-Qi; Han, Jiahuai (2015-12-01). "Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion". Cell Research. 25 (12): 1285–1298. doi:10.1038/cr.2015.139. ISSN 1001-0602. PMC 4670995. PMID 26611636.

[ced-3-17] Yuan, J; et al. (1993). "The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme". Cell. 75 (4): 641–652. doi:10.1016/0092-8674(93)90485-9. PMID 8242740.

[Alnemri_ES-18] Alnemri ES, Emad S; et al. (1996). "Human ICE/CED-3 Protease Nomenclature". Cell. 87 (2): 171. doi:10.1016/S0092-8674(00)81334-3. PMID 8861900. Retrieved 6 March 2011.

v t e Proteases: cysteine proteases (EC 3.4.22)

Caspase	Caspase 1 Caspase 2 Caspase 3 Caspase 4 Caspase 5 Caspase 6 Caspase 7 Caspase 8 Caspase 9 Caspase 10 Caspase 12 Caspase 13 Caspase 14

Fruit-derived	Papain Ficain Bromelain Actinidain

Calpain	CAPN1 CAPN2 CAPN3 CAPN5 CAPN6 CAPN7 CAPN8 CAPN9 CAPN10 CAPN11 CAPN12 CAPN13 CAPN14 CAPNS1 CAPNS2

Cathepsin	B C F H K L1/L2 O S W Z

Other	Clostripain Cancer procoagulant Separase Autophagin Cruzipain

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caspase