Property Summary

NCBI Gene PubMed Count 111
PubMed Score 276.94
PubTator Score 233.29

Knowledge Summary

Patent

No data available

Expression

Protein-protein Interaction (4)

MLP Assay (4)

AID Type Active / Inconclusive / Inactive Description
686996 screening 1854 / 3 / 346159 VEID(2) R110 Enzymatic Primary HTS to identify Inhibitors of Caspase 6 Measured in Biochemical System Using Plate Reader - 7052-01_Inhibitor_SinglePoint_HTS_Activity_Set2
687025 summary 0 / 0 / 0 Broad Institute Inhibitors of Caspase 6 Inhibitor Probe Project
720632 confirmatory 443 / 1 / 519 VEID(2) R110 Enzymatic Primary HTS to identify Inhibitors of Caspase 6 Measured in Biochemical System Using Plate Reader - 7052-01_Inhibitor_Dose_CherryPick_Activity
743332 confirmatory 3 / 0 / 31 VEID(2) R110 Enzymatic Primary HTS to identify Inhibitors of Caspase 6 Measured in Biochemical System Using Plate Reader - 7052-01_Inhibitor_Dose_DryPowder_Activity

Gene RIF (62)

PMID Text
26505998 The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11
24810717 unmodified STAT1 is cleaved at multiple sites by caspase-3 and caspase-6 in malignant undifferentiated hematopoietic cells
24727569 axon regeneration promoted by suppression of CASP2 and CASP6 is CNTF-dependent and mediated through the JAK/STAT signalling pathway
24419379 In this study, the crystal structure of a full-length CASP6 zymogen mutant, proCASP6H121A, was solved.
24363090 Caspase-6 plays a role in activating caspase-3 in Tau truncation.
24265764 Caspase-6 is likely important in most tissues during early development but is less involved in adult tissues
24070868 p53 activity is an important upstream regulator of caspase-6 activity in Huntington's disease.
24058506 Significant associations have been found between CpG sites and patient sex, including DNA methylation in CASP6, a gene that may respond to estradiol treatment, and in HSD17B12, which encodes a sex steroid hormone.
23402898 Caspase 6 activity in entorhinal cortex identifies aged individuals at risk for developing Alzheimer's disease.
22891250 binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation.
22858542 Results demonstrate that in the absence of caspase 6 activity, intrinsic triggers of apoptosis induce the receptor-interacting-kinase-1-dependent production of pro-inflammatory cytokines.
22683611 peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization
22433863 Results showed the inhibition mechanism of CASP6 phosphorylation and laid the foundation for a new strategy of rational CASP6 drug design.
22094081 Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury
21936563 Caspase-6 cleaves human TERT at residues E129 and D637 as part of the apoptosis pathway in cultured cells.
21918813 Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury
21621544 New crystal form of apo-caspase-6 is presented in canonical conformation by identifying the previous apostructure as a hydrogen-ion concentration (pH)-inactivated form of caspase-6.
21317160 Data suggest that Casp4, Casp 6 and TNFSF10 are differentially expressed in potentially fertile and subfertile men and represent useful biomarkers for predicting male fertility in combination with P1 and P2.
21111746 These data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases.
21098228 Intact IRAK-M is strongly expressed in resting alveolar macrophages but is cleaved in patients with pneumonia via neutrophil-mediated induction of CASP-6 activity.
20890311 CASP6 can be activated and regulated through intramolecular self-cleavage.
20855536 Observational study of gene-disease association. (HuGE Navigator)
20801175 Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury
20702410 a central and so far underappreciated role of caspase-8 dimerization/dissociation in avoiding unwanted cell death by lethal amplification of caspase responses via the caspase-8, -3, -6 loop.
20682790 These results imply that pro-Casp6b could negatively regulate pro-Casp6a activation in neurons and prevent Casp6a-mediated axonal degeneration.
20661084 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20606168 The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases.
20437871 Data showed that prostate cancer and PIN cells display higher expression of the proapoptotic proteins caspase-6 and BNIP3 than normal cells.
20427671 results show that p97 is cleaved by Casp6 in Alzheimer's disease and suggest p97 cleavage as an important mechanism for ubiquitin proteasome system impairment
20402676 Observational study of gene-disease association. (HuGE Navigator)
20332099 Observational study of gene-disease association. (HuGE Navigator)
20097875 Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury
19915487 Casp-6 is activated in familial forms of Alzheimer disease, as previously observed in sporadic forms.
19897582 p53 activation enhances XIAP inhibition-induced cell death by promoting mitochondrial release of second mitochondria-derived activator of caspases (SMAC) and by inducing the expression of caspase-6.
19773279 Observational study of gene-disease association. (HuGE Navigator)
19694615 The crystal structure of caspase-6, a selective effector of axonal degeneration.
19573080 Observational study of gene-disease association. (HuGE Navigator)
19414860 Observational study of gene-disease association. (HuGE Navigator)
19269008 Observational study of gene-disease association. (HuGE Navigator)
19219602 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19052714 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19022247 During hypoxia in tube-forming endothelial cells, caspase-7 is responsible for chromatin condensation and nuclear fragmentation while caspase-6 is responsible for DNA ladder formation.
18946722 Report co-localization of hyperphosphorylated tau and caspases 3/6 in the brainstem of Alzheimer's disease patients.
18820706 Caspase 6 cleaves cyclin B1 during mitotic catastrophe. Mitotic & apoptotic functions may be linked by caspase-dependent processing of mitotic activators.
18762957 Expression of caspase 6 and caspase 14 genes were different between normal skin of keloid-prone individuals and normal skin of keloid-resistant patients.
18497562 Resveratrol displays converse dose-related effects on fluorouracil-evoked colon cancer cell apoptosis: the role of CASP6 is reported.
18155731 The experiments revealed that N induces the intrinsic apoptotic pathway, resulting in processing of N at residues 400 and 403 by caspase-6 and/or caspase-3.
17392160 Active caspase-6 could be an early instigator of neuronal dysfunction.
16977583 Caspase-6 was overexpressed in 52.9% of the 210 cases studied, showing predominantly cyoplasmic with some nuclear staining.
16948818 data indicate that the CASP6 gene is occasionally mutated in gastric and colorectal carcinomas; also, the data suggest the possibility that deficiency of caspase-6 expression might contribute to the pathogenesis of gastric cancers
16518869 caspase-6 and its cleavage of lamin A are critical in apoptotic signaling triggered by resveratrol in the colon carcinoma cells, which can be activated in the absence of Bax or p53
16135563 results suggest that splitting of BL41-E95-A cells induces de novo synthesis of a protein involved in the activation of casp-6 and casp-8, which cleaves 5-LO.
16123779 results show that Csp-1 is an upstream positive regulator of Csp-6-mediated cell death in primary human neurons; also results suggest that the activation of Csp-1 must be accompanied by an apoptotic insult to induce Csp-6-mediated cell death
15654952 caspase 6 cleaves periplakin at an unconventional recognition site, amino acid sequence TVAD
15511269 caspase-2, -6 and -7 expression in gastric cancer cells is decreased compared to in normal gastric mucosal cells
15356202 CASP-6 cleaves the N terminus of tau in vitro at D13, a semicanonical and hitherto undescribed caspase cleavage site in tau. This suggests a role for caspase-6 & N-terminal truncation of tau during neurofibrillary tangle & Alzheimer's disease progression.
15321985 programmed cell death was executed by caspase 6 in Streptococcus pneumoniae infected lung epithelium
15280469 induced and utilized by human Astrovirus Yuc8 to promote processing of the capsid precursor and dissemination of the viral particles in CAC0-2 cells.
15273717 ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.
15103018 Exposure of cultured human primary astrocytes to HIV-1 Vpr induces p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury
12145703 Pro-CASP6 was the only proenzyme whose localization was limited to the cytosol in U937 cells during TPA-induced differentiation.
12089322 identified executioner caspase-6 as a transcriptional target of p53. The mechanism involves DNA binding by p53 to the third intron of the caspase-6 gene and transactivation.

AA Sequence

MSSASGLRRGHPAGGEENMTETDAFYKREMFDPAEKYKMDHRRRGIALIFNHERFFWHLTLPERRGTCAD      1 - 70
RDNLTRRFSDLGFEVKCFNDLKAEELLLKIHEVSTVSHADADCFVCVFLSHGEGNHIYAYDAKIEIQTLT     71 - 140
GLFKGDKCHSLVGKPKIFIIQACRGNQHDVPVIPLDVVDNQTEKLDTNITEVDAASVYTLPAGADFLMCY    141 - 210
SVAEGYYSHRETVNGSWYIQDLCEMLGKYGSSLEFTELLTLVNRKVSQRRVDFCKDPSAIGKKQVPCFAS    211 - 280
MLTKKLHFFPKSN                                                             281 - 293
//

Text Mined References (113)

PMID Year Title
26505998 2015 Sox11 Reduces Caspase-6 Cleavage and Activity.
25416956 2014 A proteome-scale map of the human interactome network.
24810717 2014 Caspase-3 and caspase-6 cleave STAT1 in leukemic cells.
24727569 2014 Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling.
24419379 2014 The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays.
24363090 2014 A synergic role of caspase-6 and caspase-3 in Tau truncation at D421 induced by H2O 2.
24265764 2013 Expression and activation of caspase-6 in human fetal and adult tissues.
24070868 2014 p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin.
24058506 2013 Genetic effects on DNA methylation and its potential relevance for obesity in Mexican Americans.
23402898 2013 Caspase-6 activity predicts lower episodic memory ability in aged individuals.
22891250 2012 Zinc-mediated allosteric inhibition of caspase-6.
22858542 2013 Intrinsic cleavage of receptor-interacting protein kinase-1 by caspase-6.
22683611 2012 Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.
22433863 2012 Inhibitory mechanism of caspase-6 phosphorylation revealed by crystal structures, molecular dynamics simulations, and biochemical assays.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21936563 2011 The catalytic subunit of human telomerase is a unique caspase-6 and caspase-7 substrate.
21621544 2011 A new apo-caspase-6 crystal form reveals the active conformation of the apoenzyme.
21492153 2011 Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2.
21317160 2011 Apoptotic gene expression in potentially fertile and subfertile men.
21269460 2011 Initial characterization of the human central proteome.
21111746 2011 Substrate-induced conformational changes occur in all cleaved forms of caspase-6.
21098228 2011 Neutrophils activate alveolar macrophages by producing caspase-6-mediated cleavage of IL-1 receptor-associated kinase-M.
20890311 2010 Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation.
20855536 2010 Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.
20702410 2010 The caspase-8 dimerization/dissociation balance is a highly potent regulator of caspase-8, -3, -6 signaling.
20682790 2010 Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A.
20661084 2010 Polymorphisms in the caspase genes and the risk of lung cancer.
20606168 2010 Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition.
20437871 Expression analysis of caspase-6, caspase-9 and BNIP3 in prostate cancer.
20427671 2010 Identification of Caspase-6-mediated processing of the valosin containing protein (p97) in Alzheimer's disease: a novel link to dysfunction in ubiquitin proteasome system-mediated protein degradation.
20402676 2010 Mutational analysis of caspase genes in prostate carcinomas.
20332099 2010 A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts.
19915487 2009 Caspase-6 activation in familial alzheimer disease brains carrying amyloid precursor protein or presenilin i or presenilin II mutations.
19897582 2010 Simultaneous activation of p53 and inhibition of XIAP enhance the activation of apoptosis signaling pathways in AML.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19694615 2009 The crystal structure of caspase-6, a selective effector of axonal degeneration.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19414860 2009 Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.
19269008 2009 Mutational analysis of CASP1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 14 genes in gastrointestinal stromal tumors.
19219602 2009 Prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) 8473T>C polymorphism associated with prognosis for patients with colorectal cancer treated with capecitabine and oxaliplatin.
19052714 2009 TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin.
19022247 2009 Possible involvement of caspase-6 and -7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells.
18946722 2009 Co-localization of hyperphosphorylated tau and caspases in the brainstem of Alzheimer's disease patients.
18820706 2009 Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe.
18762957 2009 Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients.
18497562 2008 Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: the roles of caspase-6 and p53.
18408014 2008 SUMO conjugation to the matrix attachment region-binding protein, special AT-rich sequence-binding protein-1 (SATB1), targets SATB1 to promyelocytic nuclear bodies where it undergoes caspase cleavage.
18155731 2008 Cell type-specific cleavage of nucleocapsid protein by effector caspases during SARS coronavirus infection.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17392160 2007 Activation of caspase-6 in aging and mild cognitive impairment.
17167422 2007 Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1.
16977583 2006 Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study.
16948818 2006 Mutational analysis of the CASP6 gene in colorectal and gastric carcinomas.
16518869 2006 Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop.
16341674 2005 Transcriptome analysis of human gastric cancer.
16135563 2005 Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells.
16123779 2006 Caspase-1 activation of caspase-6 in human apoptotic neurons.
15735701 2005 Caspase-9 can antagonize p53-induced apoptosis by generating a p76(Rb) truncated form of Rb.
15654952 2005 Breaking the connection: caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region.
15511269 2004 Loss of caspase-2, -6 and -7 expression in gastric cancers.
15500642 2004 Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15356202 2004 Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease.
15321985 2004 Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium.
15280469 2004 Caspases mediate processing of the capsid precursor and cell release of human astroviruses.
15273717 2004 Regulation of caspase-6 and FLIP by the AMPK family member ARK5.
15200957 2004 Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase.
12888622 2003 Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12232792 2002 Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain.
12145703 2002 Intracellular redistribution of procaspases during TPA-induced differentiation of U937 human leukemic cells.
12089322 2002 Apoptotic threshold is lowered by p53 transactivation of caspase-6.
12052891 2002 Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase alpha during farnesol-induced apoptosis.
11953316 2002 Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation.
11901153 2002 Protein kinase C-beta II Is an apoptotic lamin kinase in polyomavirus-transformed, etoposide-treated pyF111 rat fibroblasts.
11802788 2002 The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis.
11514563 2001 Identification of a caspase-9 substrate and detection of its cleavage in programmed cell death during mouse development.
11463840 2001 SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.
11438643 2001 Transcription factor AP-2alpha is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor alpha-induced apoptosis in breast cancer cells.
11423904 2001 Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis.
11387340 2001 Serum response factor cleavage by caspases 3 and 7 linked to apoptosis in human BJAB cells.
11356849 2001 Effect of mutation and phosphorylation of type I keratins on their caspase-mediated degradation.
11331782 2001 Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis.
11262188 2001 Comprehensive studies on subcellular localizations and cell death-inducing activities of eight GFP-tagged apoptosis-related caspases.
11246070 2001 Cloning and sequencing of caspase 6 in rainbow trout, Oncorhynchus mykiss, and analysis of its expression under conditions known to induce apoptosis.
11098060 2001 TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis.
10770929 2000 Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells.
10734073 2000 Identification of caspase 3-mediated cleavage and functional alteration of eukaryotic initiation factor 2alpha in apoptosis.
10655504 2000 HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.
10481058 1999 Proteolytic cleavage of beta-catenin by caspases: an in vitro analysis.
10469173 1999 Changes in nuclear morphology during apoptosis correlate with vimentin cleavage by different caspases located either upstream or downstream of Bcl-2 action.
10438520 1999 Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease.
10432301 1999 Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2alpha.
10409650 1999 Alternative, non-secretase processing of Alzheimer's beta-amyloid precursor protein during apoptosis by caspase-6 and -8.
10205159 1999 Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis.
10069390 1999 Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases.
9990034 1999 Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis.
9933635 1999 Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis.
9857079 1998 The 72-kDa component of signal recognition particle is cleaved during apoptosis.
9593687 1998 Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis.
9463409 1998 Caspases are activated in a branched protease cascade and control distinct downstream processes in Fas-induced apoptosis.
9337844 1997 Caspases: the executioners of apoptosis.
9298992 1997 Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis.
9228018 1997 FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.
9219695 1997 Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease.
8978814 1996 Lamin proteolysis facilitates nuclear events during apoptosis.
8962078 1996 Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases.
8900201 1996 The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32.
8812467 1996 Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3.
8780721 1996 Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis.
8710882 1996 Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis.
7983002 1994 CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
7796396 1995 Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family.