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貨期:
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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Cysteine protease that plays essential roles in programmed cell death, axonal degeneration, development and innate immunity. During apoptosis, localizes in the nucleus and cleaves the nuclear structural protein NUMA1 and lamin A/LMNA thereby inducing nuclear shrinkage and fragmentation. Furthermore, cleaves many transcription factors such as NF-kappa-B and cAMP response element-binding protein/CREBBP. Cleaves phospholipid scramblase proteins XKR4 and XKR9. Plays an essential role in axon degeneration during axon pruning which is the remodeling of axons during neurogenesis but not apoptosis. Regulates B-cell programs both during early development and after antigen stimulation. In addition, promotes the ZBP1-mediated activation of programmed cell death pathways including pyroptosis, apoptosis, and necroptosis (PANoptosis) and plays an essential role in defense against viruses. Mechanistically, interacts with RIPK3 and enhances the interaction between RIPK3 and ZBP1, leading to ZBP1-mediated inflammasome activation and cell death.
基因功能參考文獻:
The prodomain region was found to be intrinsically disordered independent of the activation state of caspase-6; however, its complete removal resulted in the protection of the adjacent 26-32 region, suggesting that this region may play a regulatory role. The molecular details of caspase-6 dynamics in solution provide a comprehensive scaffold for strategic design of therapeutic approaches for neurodegenerative disorders. PMID: 28864531
SMSr is a novel and specific substrate of caspase-6, a non-conventional effector caspase implicated in Huntington's and Alzheimer's diseases. PMID: 28659495
Results support the possibility that the Casp6 activity in the anterior olfactory nucleus of the olfactory bulb reflects degeneration in the entorhinal cortex and suggest that Casp6 activity in the olfactory bulb could represent degeneration associated with cognitive decline and early Alzheimer disease. PMID: 27931265
These data suggest that caspase-6 deactivating mutations may contribute to multifactorial carcinogenic transformations. PMID: 28726391
Caspase-6 undergoes helix-strand transition upon substrate binding. Caspase-6 shows distinctive conformational dynamics in its 130's region Local pKa Values of Key Amino Acid Residues within the 130's Region Vary between the Unliganded (Helical) and the VEID-bound (Strand) States of Caspase-6 . PMID: 28154009
Following specific binding to and internalization into HER2-overexpressing tumor cells, the e23sFv-Fdt-casp6 protein induced tumor cell apoptosis and inhibited the proliferation of HER2-overexpressing A172 and U251MG cells in vitro, but not in U87MG cells with undetectable HER2 PMID: 27633091
Results identified novel members of the CASP6 interactome and demonstrate that a number of them are involved in key signaling pathways observed in neurodegenerative diseases. PMID: 26908611
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 PMID: 26505998
Caspase-6 plays a role in activating caspase-3 in Tau truncation. PMID: 24363090
p53 activity is an important upstream regulator of caspase-6 activity in Huntington's disease. PMID: 24070868
In this study, the crystal structure of a full-length CASP6 zymogen mutant, proCASP6H121A, was solved. PMID: 24419379
Caspase-6 is likely important in most tissues during early development but is less involved in adult tissues PMID: 24265764
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. PMID: 24058506
Caspase 6 activity in entorhinal cortex identifies aged individuals at risk for developing Alzheimer's disease. PMID: 23402898
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. PMID: 22858542
binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation. PMID: 22891250
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 PMID: 22683611
Results showed the inhibition mechanism of CASP6 phosphorylation and laid the foundation for a new strategy of rational CASP6 drug design. PMID: 22433863
Caspase-6 cleaves human TERT at residues E129 and D637 as part of the apoptosis pathway in cultured cells. PMID: 21936563
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. PMID: 21621544
These data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases. PMID: 21111746
CASP6 can be activated and regulated through intramolecular self-cleavage. PMID: 20890311
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. PMID: 21098228
These results imply that pro-Casp6b could negatively regulate pro-Casp6a activation in neurons and prevent Casp6a-mediated axonal degeneration. PMID: 20682790
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. PMID: 20606168
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 PMID: 20427671
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. PMID: 19897582
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. PMID: 12089322
Pro-CASP6 was the only proenzyme whose localization was limited to the cytosol in U937 cells during TPA-induced differentiation. PMID: 12145703
ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system. PMID: 15273717
programmed cell death was executed by caspase 6 in Streptococcus pneumoniae infected lung epithelium PMID: 15321985
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. PMID: 15356202
caspase 6 cleaves periplakin at an unconventional recognition site, amino acid sequence TVAD PMID: 15654952
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. PMID: 16135563
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 PMID: 16948818
Caspase-6 was overexpressed in 52.9% of the 210 cases studied, showing predominantly cyoplasmic with some nuclear staining. PMID: 16977583
Active caspase-6 could be an early instigator of neuronal dysfunction. PMID: 17392160
Resveratrol displays converse dose-related effects on fluorouracil-evoked colon cancer cell apoptosis: the role of CASP6 is reported. PMID: 18497562
Expression of caspase 6 and caspase 14 genes were different between normal skin of keloid-prone individuals and normal skin of keloid-resistant patients. PMID: 18762957
Caspase 6 cleaves cyclin B1 during mitotic catastrophe. Mitotic & apoptotic functions may be linked by caspase-dependent processing of mitotic activators. PMID: 18820706
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. PMID: 19022247
The crystal structure of caspase-6, a selective effector of axonal degeneration. PMID: 19694615
Casp-6 is activated in familial forms of Alzheimer disease, as previously observed in sporadic forms. PMID: 19915487