key: cord-0036809-3wyq847h
authors: nan
title: Caspase-6
date: 2009-10-01
journal: Class 3 Hydrolases
DOI: 10.1007/978-3-540-85705-1_13
sha: 35feaf3f7365976866579a14defb12be6c8de442
doc_id: 36809
cord_uid: 3wyq847h

nan

Natural substrates and products S SATB1 + H 2 O <3> (<3> cleavage disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis [13] ) (Reversibility: ?) [13] P ? S Ufd2p + H 2 O <3> (<3> cleavage of polyubiquitination factor Ufd2p at Asp123 within the putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade [14] ) (Reversibility: ?) [14] P ? S b-catenin + H 2 O <2> (<2> processing of b-catenin, production of a 70000

Da fragment [8] ) (Reversibility: ?) [8] P ? S lamin A + H 2 O <3> (<3> cleavage site is VEID-/- [7] ) (Reversibility: ?)

[7] P ? S poly(ADP-ribose)polymerase + H 2 O <6> (<6> the enzyme may participate in poly(ADP-ribose)polymerase cleavage observed during apoptosis [9] ) (Reversibility: ?) [9] P ? S pro-caspase-6 + H 2 O <3> (<3> caspase-8 activates caspase-3, and caspase-3 in turn activates caspase-6. Caspase 3 has a major role in nuclear apoptosis [20] ) (Reversibility: ?) [20] P ? S pro-caspase-8 + H 2 O <3> (<3> caspase-6 is the major activator of caspase-8 in the cytochrome c-induced apoptosis pathway. Caspase-8 precursor is initially cleaved between the p18 and p10 domains resulting in fragments of 42000 Da and 10000 Da. The 42000 Da fragment is further cleaved resulting in fragments of 25000 Da and 18000 Da [11] ) (Reversibility: ?) [ [9] ; <3> the preferred cleavage sequence is VEHD-/- [6, 7] ; <7> overexpression induces apoptosis [10] ; <3> the enzyme has a major role in nuclear apoptosis [20] ) (Reversibility: ?) [6, 7, 9, 10, 20 ] P ?

4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-Leu-vinylsulfone <3> [25] DMSO <3> [30] IETD-CHO <2> (<2> caspase-6 in lens extracts from neonatal mice partially inhibited by 0.0005 mM [25] ) [25] VEID-CHO <2> (<2> caspase-6 in lens extracts from neonatal mice efficiently inhibited by 0.0005 mM [25] ) [25] VEID-FMK <3> [30] Z-VEID-fmk <3> [31] Z-Val-Ala-ASp-fluoromethylketone <3> (<3> inhibitor of caspases [24] ) [24, 26, 29, 31] ZVEID <3> (<3> specific caspase 6 inhibitor [24] ) [24] ZVEID-fmk <3> (<3> caspase 6-specific inhibitor, reduces apoptosis and prevents periplakin cleavage in adherent cells, although it does not completely prevent cells from detaching [26] ) [26] acetyl-AEVD-aldehyde <3> [4] acetyl-DEVD-aldehyde <3> [4] acetyl-IETD-aldehyde <3> [4] acetyl-Val-Ile-Asp-aldehyde <3> [20] acetyl-WEHD-aldehyde <3> [4] benzyloxycarbonyl-DRHD-fluoromethylketone <3> [16] benzyloxycarbonyl-VAD-fluoromethylketone <3> (<3> t 1=2 at 0.001 mM is 98 s [4] ) [4, 16] benzyloxycarbonyl-VEID-fluoromethylketone <3> [16] b-lactone <3> [25] epoxomicin <3> [25] lactacystin <3> [25] siRNA <3> (<3> silencing of caspase-6 expression [31] ) [31] Additional information <3> (<3> K i -value above 0.01 mM for acetyl-YVADaldehyde [4] ) [4] Activating compounds adriamycin <3> (<3> increases caspase-6 mRNA levels in HCT116 p53+ and neo cells but not in E6 cells [30] ) [30] P53 <3> [30] tumor necrosis factor a <3> (<3> activates caspase-6 which in turn cleaves transcription factor AP2a [16] ) [16] etopside <3> (<3> mild induction of the enzyme in HCT116 p53+ cells [30] ) [30] resveratrol <3> (<3> induces caspase-6-dependent cleavage of lamin A [31] ) [31] Turnover number (min -1 ) Additional information <3> [18] Specific activity (U/mg) Additional information <4> (<4> VEID-7-amido-4-trifluoromethylcoumarin cleavage acitivity overall increases by 6.1fold between E15.5 and E18.5 rat embryos [25] ) [ Subunits dimer <3> (<3> procaspase 6, SDS-PAGE, chemical cross-linking and gel filtration, nearly identical CD spectra of rCaspase 6 and D316A caspase 6, indicating that overal structures of both precursor and mature forms of caspase 6 should be almost indistinguishable [22] ) [22] Posttranslational modification proteolytic modification <3> (<3> the activation site is TEVD-/-(P4,P3,P2,P1) [7] ; <3> viral nucleocapsid protein of transmissible gastroenteritis coronavirus triggers the processing of procaspase 6 in human rectal tumor cell line HRT18jap1 [12] ; <3> caspase-6 is inactive until the short 23 amino acid prodomain is removed [11] ) [7, 11, 12] 5 Isolation/Preparation/Mutation/Application Source/tissue DLD-1 cell <3> [30] HCT-116 cell <3> (<3> variants p53+, p53-, Bax+, Bax- [31] ) [30, 31] HRT-18 cell <3> [12] JURKAT cell <3, 6> (<3> fas-stimulated [20] ) [9, 13, 20] Jurkat E-61 cell <3> (<3> leukemic T cell line [11] ) [11] MDCK cell <3> [26] SW-480 cell <3> [30] T-cell <6> [9] T-cell leukemia cell <3> [23] alveolar cell <3> (<3> A549 cell line infected by unencapsulated Streptococcus pneumoniae type 2 strain R6x and capsulated Streptococcus pneumoniae strain D39 and the pneumolysin-deficient R6xply mutant [24] ) [24] brain <3, 7> (<7> low activity [10] ) [10, 21, 27] breast cancer cell <3> [16] bronchial epithelial cell line <3> (<3> BEAS-2B cell line infected by unencapsulated Streptococcus pneumoniae type 2 strain R6x [24] ) [24] colorectal cancer cell line <3> [29] dentate gyrus <4> (<4> in the inner molecular layer [28] ) [28] fiber <4> (<4> primary fiber cells [25] ) [25] heart <7> [10] hippocampal pyramidal layer <4> (<4> CA1 and CA3a region [28] ) [28] kidney <7> [10] lens <2, 4> [25] leukemia cell <3> (<3> THP-1 human monocytic cell culture [25] ) [25] liver <7> [10] lung <6, 7> [1, 10] lung epithelium <3> [24] lymphocyte <6> [2] lymphoma cell <1> (<1> parental and caspase-6-DT40 chicken lymphoma cells [23] ) [23] neurofibrillary tangles <3> [21] neuron <4> (<4> hilar neurons, in the somata and in dendrites [28] ) [28] prostate cancer cell <3> [23] skeletal muscle <7> (<7> low activity [10] ) [10] spleen <7> [10] testis <7> [10] Additional information <3> (<3> p53 up-regulates caspase -6mRNA in H460, H460-neo, H460-E6, HCT16-neo, HCT16-E6, HCT16-P53-, SKBR3, U2OS, M3, HCC1937 and SW13 cell lines, MCF7 cells fail to show induction of caspase 6-mRNA [30] ; <3> present in neurophil threads and neuritic plaques, not in the cerebellum [21] ; <3> temporal and frontal cortex [21] ) [21, 30] Localization nucleus <3, 4> [23, 25] soluble <3> [11] Additional information <3> (<3> active Csp-6 is not present in the nuclei of Alzheimer's disease neurons [21] ) [21] Purification <3> [5, 11, 21, 26] <3> (purified to homogeneity) [22] Cloning <3> [4, 5, 17] <3> (cloned into pET-23 bacterial expression vector) [26] <3> (expression in Escherichia coli) [22] <3> (inserted into the pIVEX vector) [21] <5> [3] <6> [9] <7> [10] Engineering D316A <3> (<3> to prevent autocatalytic processing of the specific site of procaspase 6, Asp316 of rCaspase 6 is replaced with Ala [22] ) [22] S257A <3> (<3> mutant caspase-6, not phosphorylated in the presence of active AMPK-related kinase 5 [29] ) [29] W175F <3> (<3> reduced autocatalytic processing activity [22] ) [22] Application medicine <1, 2, 3, 4> (<4> caspase 6 expression remains elevated long after the occurrence of acute cell death during epileptogenesis and epilepsy, indicating that the enzyme has functions other than execution of programmed cell death in epileptogenic hippocampus [28] ; <3> caspase-6 is active early in the pathogenesis of Alzheimer's disease, the enzyme is strongly implicated in human neuronal degeneration and apoptosis, its inhibition may be an efficient treatment [21] ; <3> caspase-6 is phosphorylated by AMP-activated protein kinase related kinase 5 at Ser257 in colorectal cancer cells, leading to inactivation of caspase-6 and resulting in resistance to cell death via cFLIPs protection and leading to resistance to the FAS ligand/Fas system [29] ; <3> caspase-6 is upregulated in response to p53 overexpression, induction of caspase-6 expression lowers the cell death threshold in response to apoptotic signals that activate caspase-6, potential mechanism of lowering the death threshold, which could be important for chemosensitization [30] ; <3> critical role of caspase-6 and its cleavage of lamin A in apoptotic signaling triggered by resveratrol in the colon carcinoma cells [31] ; <2,4> difference between normal fiber cell differentation and apoptosis and the capacity of the lens to differentially regulate these two processes [25] ; <3> role for caspase-6 and Nterminal truncation of tau during neurovibrillary tangle evolution and the progression of Alzheimer's disease [27] ; <3> Streptococcus pneumoniae induces apoptosis of human alveolar and bronchial epithelial cells, programmed cell death is excecuted by caspase 6, and can be blocked by overexpression of Bcl2 [24] ; <1> the loss of caspase-6 does not appear to impair the ability of any anticancer agents to induce apoptosis [23] ) [21, 23, 24, 25, 27, 28, 29, 30, 31] 

Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences

The Ced-3/interleukin 1b converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2a are substrates for the apoptotic mediator CPP32

Structure, expression, and function of the Xenopus laevis caspase family

Inhibition of human caspases by peptide-based and macromolecular inhibitors

Purification and catalytic properties of human caspase family members

Proteases from cell suicide: functions and regulation of caspases. Microbiol

A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis

Proteolytic cleavage of b-catenin by caspases: an in vitro analysis

Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family

Characterization of seven murine caspase family members

Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain

The viral nucleocapsid protein of transmissible gastroenteritis coronavirus (TGEV) is cleaved by caspase-6 and -7 during TGEV-induced apoptosis

SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis

The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis

Transcription factor AP-2a is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor a-induced apoptosis in breast cancer cells

Sequence-based discovery of a synthetic peptide inhibitor of caspase 6

Molecular cloning and functional characterization of MCH2, a novel human MCH receptor

Substrate specificities of caspase family proteases

Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis

Caspases are activated in a branched protease cascade and control didtinct downstream processes in fas-induced apoptosis

Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease

The structure of procaspase 6 is similar to that of active mature caspase 6

Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis

Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium

Temporal regulation of VEID-7-amino-4-trifluoromethylcoumarin cleavage activity and caspase-6 correlates with organelle loss during lens development

Breaking the connection: caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region

Binder, L.I.: Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease

Caspase 6 expression in the rat hippocampus during epileptogenesis and epilepsy

Regulation of caspase-6 and FLIP by the AMPK family member ARK5

Apoptotic threshold is lowered by p53 transactivation of caspase-6

Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop