| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Using recombinant caspases and granzyme B , we determined that pro IL 16 cleavage is mediated only by caspase 3 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase 3 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Activation of the apoptotic protease CPP 32 by cytotoxic T cell derived granzyme B . ^^^ Here we show that granzyme B cleaves and activates CPP 32 , the precursor of the protease responsible for cleavage of poly ( ADP ribose ) polymerase . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Recent studies suggest that granzyme B may exert its effect by cleaving and activating CPP 32 , a member of the interleukin 1 beta converting enzyme / Ced 3 family of cysteine proteases . ^^^ We have examined the processing and activation of CMH 1 , a close homologue of CPP 32 , by granzyme B in vitro . ^^^ The cleavage and activation of CMH 1 by granzyme B in vitro sugge st that , in addition to CPP 32 , CMH 1 may also play a role in CTL mediated cell killing . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The cytotoxic cell protease granzyme B initiates apoptosis in a cell free system by proteolytic processing and activation of the ICE / CED 3 family protease , CPP 32 , via a novel two step mechanism . ^^^ Granzyme B induced apoptosis was neutralized by a tetrapeptide inhibitor of the ICE / CED 3 family protease , CPP 32 , whereas a similar inhibitor of ICE had no effect . ^^^ Granzyme B was found to convert CPP 32 , but not ICE , to its active form by cleaving between the large and small subunits of the CPP 32 proenzyme , resulting in removal of the prodomain via an autocatalytic step . ^^^ The cowpox virus protein CrmA , a known inhibitor of ICE family proteases as well as granzyme B , inhibited granzyme B mediated CPP 32 processing and apoptosis . ^^^ These data demonstrate that CPP 32 activation is a key event during apoptosis initiated by granzyme B . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that granzyme B processes interleukin 1beta converting enzyme ( ICE ) and the ICE related protease Yama ( also known as CPP 32 or apopain ) by limited proteolysis . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Cleavage of CPP 32 by granzyme B represents a critical role for granzyme B in the induction of target cell DNA fragmentation . ^^^ One family member , CPP 32 , has been identified as an intracellular substrate for granzyme B , a CTL specific serine protease responsible for the early induction of target cell DNA fragmentation . ^^^ Here we use cytolytic cells from granzyme B deficient mice to confirm that cleavage and activation of CPP 32 represents a nonredundant role for granzyme B and that this activation plays a role in the induction of DNA fragmentation in target cells , a signature event for apoptotic cell death . ^^^ A peptide inhibitor of CPP 32 like proteases confirmed the function of these enzymes in fragmentation . 51Cr release was not suppressed under these conditions , suggesting that granzyme B cleavage of CPP 32 is primarily involved in the induction of DNA fragmentation and not membrane damage during CTL induced apoptosis . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Furthermore , incubation of DNA PKcs with granzyme B did not produce the same cleavage pattern observed in cells undergoing apoptosis and when this substrate was incubated with either CTL extracts or the ICE like protease , CPP 32 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Here we show that in cells undergoing apoptosis by granzyme B , both p 45 pro interleukin 1 beta converting enzyme ( ICE ) and pro CPP 32 are processed . ^^^ In ICE / B cells or HeLa cells transfected with mutant inactive ICE or Ich 1S that exhibit resistance to granzyme B , CPP 32 is processed to p 17 and poly ( ADP ribose ) polymerase is cleaved indicating that this protease although activated was not associated with an apoptotic nuclear phenotype . ^^^ We conclude that granzyme B activates an ICE dependent cell death pathway in some cell types and requires a CPP 32 like Ac DEVD CHO inhibitable protease acting upstream to initiate apoptosis . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Granzyme B at a concentration that allows processing and activation of CPP 32 failed to process pro Mch2alpha . ^^^ However , incubation of pro Mch2alpha with granzyme B in the presence of a cellular extract containing pro CPP 32 resulted in activation of pro CPP 32 and subsequent processing of pro Mch2alpha . ^^^ Interestingly , granzyme B can also process pro Mch 6 but at a site N terminal to that cleaved by CPP 32 . ^^^ These data suggest that Mch2alpha and Mch 6 are downstream proteases activated in CPP 32 and granzyme B mediated apoptosis . ^^^ This is the first demonstration of a protease cascade involving granzyme B , CPP 32 , Mch2alpha , and Mch 6 and evidence that the lamin cleaving enzyme Mch 2 is a target of mature CPP32 . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Using recombinant ICE like proteases and purified hnRNP C proteins in vitro , we show that the C proteins are cleaved by Mch3alpha and CPP 32 and , to a lesser extent , by Mch2alpha , but not by ICE , Nedd 2 , Tx , or the cytotoxic T cell protease granzyme B . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Inhibition of CPP 32 like proteases prevents granzyme B and Fas , but not granzyme A based cytotoxicity exerted by CTL clones . ^^^ It has been reported that granzyme B can cleave and activate the apoptotic cysteine protease p 32 ( CPP 32 ) / Yama and its homologues in vitro . ^^^ These results suggest that granzyme B and Fas based cytotoxicity exerted by CTL clones converge at the level of CPP 32 like protease activation , while granzyme A acts via a different , still undefined , pathway . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Our results reveal that the proforms of the CASP 3 subfamily members mCASP 3 and mCASP 7 are hydrolyzed by granzyme B , while proforms of CASP 2 and CASP 1 subfamily members are not directly cleaved . ^^^ Only one CASP 3 subfamily member , pro mCASP 6 , was not proteolytically cleaved by granzyme B . ^^^ These results indicate that two members of the CASP 3 subfamily , but no others , become activated by granzyme B . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Direct cleavage and activation of caspase 3 and related proteases by granzyme B have been identified as a central event in apoptosis induction by cytotoxic granules . ^^^ Thus , Bcl 2 antagonizes granzyme B mediated apoptosis by a mechanism that interferes with caspase 3 activity . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| We investigated whether p 53 dependent apoptosis requires activation of CPP32beta ( caspase 3 ) , a cysteine protease that has been found to mediate apoptosis in response to ligation of the Fas molecule or to granzyme B , a component of CTL lytic granules . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Since the granzyme B is a direct activator of caspase 3 and its expression is induced following T cell activation , we tested the effects of anti GraB , an engineered serpin that specifically inhibits GraB . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The sites were mapped to DQTD 772 , which was preferentially cleaved by caspase 3 , and VSWD 704 , which was preferentially cleaved by caspase 6 and cytotoxic T lymphocyte derived granzyme B . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Caspase 3 activation is primarily the result of the direct action of granzyme B . ^^^ Our results demonstrate that whereas Fas mediated activation of caspase 3 requires an upstream caspase activity that is zVAD fmk sensitive , the initial cleavage of caspase 3 during granule mediated cell death is insensitive to zVAD fmk , suggesting that caspase 3 is cleaved directly by granzyme B in vivo . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The preferred substrate sequence matches the activation sites of caspase 3 and caspase 7 and thus is consistent with the role of granzyme B in activation of these proteases during apoptosis . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Importantly , IL 2 was determined in cell culture supernatants , thus avoiding a cell lysis step that might have enabled activation of caspase 3 by granzyme B . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| In contrast to many other caspase family members , murine caspase 14 is not cleaved by granzyme B , caspase 1 , caspase 2 , caspase 3 , caspase 6 , caspase 7 or caspase 11 , but is weakly processed into p 18 and p 11 subunits by murine caspase 8 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The apoptotic pathway distal to the DISC is intact because ceramide analogs , staurosporine , and granzyme B activate caspase 3 and induce apoptosis . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Strikingly , only the DEVD cleaving caspases , caspase 3 and caspase 7 , inactivated DFF45 / ICAD and promoted DNA fragmentation in an in vitro DFF40 / CAD assay , suggesting that granzyme B , caspase 6 , and caspase 8 promote DFF45 / ICAD inactivation and DNA fragmentation indirectly by activating caspase 3 and / or caspase 7 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| These results provide evidence for a two pronged strategy for mediating target cell destruction and provide evidence of a direct link between granzyme B activity , Bid cleavage , and caspase 3 activation in whole cells . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The LAK cell enhanced caspase 3 activity in the pretreated OSC 3 cells was decreased to approximately 70 % and 40 % of the control by the addition of Z AAD CMK ( a granzyme B inhibitor ) and neutralising monoclonal antibody to Fas antigen ( alphaFas IgG ) , respectively . ^^^ These results indicate that anticancer drugs and gamma rays prime squamous cell carcinoma cells to be susceptible to apoptosis by LAK cells , that LAK cell induced apoptosis largely depends on the activation of caspase 3 by the Fas / Fas ligand signal and granzyme B , and that LAK cells induce ROI in the target cells , which is largely mediated by Fas and granzyme B . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Second , the delivery system mediated delivery of several caspases ( caspase 3 , caspase 8 , and granzyme B ) into cultured cell lines and primary cells triggering apoptosis . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The aims of this study were to determine whether CC cells are also resistant to perforin / granzyme B and whether the FasL resistance lies upstream of caspase 3 activation . ^^^ Since both the FasL and perforin / granzyme B pathways converge at caspase 3 , we measured caspase 3 activity to learn whether the FasL resistance was due to failure to activate this crucial executioner . ^^^ Caspase 3 activation occurred in CC531s cells after perforin / granzyme B treatment , but not after the addition of recombinant FasL . ^^^ Furthermore , we showed that caspase 3 activity is involved in the execution of perforin / granzyme B induced apoptosis in CC 531 s cells , since the cell permeable caspase 3 inhibitor Z DEVD FMK abrogated DNA fragmentation . ^^^ Together , these results suggest that CC cells are sensitive to perforin / granzyme B induced apoptosis by activating caspase 3 and FasL resistance lies upstream of this executioner caspase . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Anti beta fodrin Abs in patients ' sera as well as mouse polyclonal sera raised against the amino terminal beta fodrin fragment did not react with intact beta fodrin , but recognized the 65 kDa amino terminal fragment generated through cleavage by caspase 3 or granzyme B . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Inhibition of trypsin like ( plasmin , granzyme A , and thrombin ) and caspase like ( granzyme B ) serine proteases was not observed or highly inefficient ( trypsin ) , nor was inhibition of proteases from the cysteine ( caspase 1 and caspase 3 ) and metalloprotease ( macrophage elastase , MMP 12 ) families . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemical demonstration of the expression of th following markers was performed on formalin fixed skin sections : Fas ( CD 95 ) , Fas ligand ( FasL ) bcl 2 , granzyme B , the tumour suppressor protein PTEN and the effector caspase , caspase 3 . ^^^ The apoptosis associated marker Fas , FasL , caspase 3 and granzyme B were expressed by morphologically neoplastic cells in CTCL and by large atypical cells in LyP , with no significant differences . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Actual execution of apoptosis depends on proper functioning of effector caspases , particularly caspase 3 , and on the expression levels of apoptosis regulating proteins , including Bcl 2 and the recently identified granzyme B specific protease inhibitor 9 ( PI 9 ) . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| We mapped a major autoimmune epitope in XRCC 4 and found that it encompassed a DNA dependent protein kinase phosphorylation site , which is located at serine 260 ; that it was adjacent to a site for caspase 3 , which cleaves after residue 265 ; and that it also spanned a site for the inflammatory protease , granzyme B , which cleaves after residue 254 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Thus granzyme B mediates direct cleavage of caspase 3 and also activates mitochondrial disruption , resulting in the release of proapoptotic proteins that suppress caspase inhibition . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Once in the cytosol , granzyme B targets caspase 3 directly or indirectly through the mitochondria , initiating the caspase cascade to DNA fragmentation and apoptosis . ^^^ Recent work shows that granzyme B mediated release of apoptotic factors from the mitochondria is essential for the full activation of caspase 3 . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Treatment of HL 60 cells with lactacystin , a selective inhibitor of the proteasome , exponentially increased caspase 3 like hydrolytic activity and induced apoptosis but had little or no effect on the activity of upstream caspase 8 , caspase 9 , or granzyme B . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| RT PCR , immunoblotting and immunohistochemistry were used to study the samples for the expression of apoptotic cells , perforin , granzyme B , Fas , Fas ligand and caspase 3 . ^^^ Perforin / granzyme B and caspase 3 were expressed consistently , however Fas ligand was not . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| We show that granzymes A and B and the granzyme B substrate , caspase 3 , are important for regulating gammaHV 68 latent infection . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| We show that granzyme B initiates a two tiered caspase activation cascade involving seven caspases , where caspase 3 is required for the second tier of caspase activation events . ^^^ Using a two dimensional gel based proteomics approach we have also examined the scale of granzyme B initiated alterations to the proteome in the presence or absence of effector caspase 3 or 7 . ^^^ These studies indicate that granzyme B targets a highly restricted range of substrates and orchestrates cellular demolition largely through activation of caspase 3 . . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Flowcytometric analysis was performed after staining for surface CD 4 , CD 8 , and CD 25 and for intracellular perforin , granzyme B , active caspase 3 , and TGF beta . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| The DS brain was examined using immunocytochemistry and antibodies against the active fragment of caspase 8 ( AC , 8 ) and to caspase 3 cleavage products of fodrin ( CCP ) , a neuronal cytoskeleton protein . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Both BCP and CCP increased caspase 3 activity as compared with controls , but CCP caused more activation of caspase 3 than BCP ( 6 . 2 + / 0 . 7 fold vs 3 . 1 + / 0 . 4 , p < 0 . 05 ) . ^^^ CONCLUSIONS : Blood cardioplegia is superior to CCP in inhibiting the activation of caspase 3 and in increasing phospho Bad . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| Both BKPC and CCP alone increased caspase 3 cleavage and activity as compared with controls ( P < 0 . 05 and P < 0 . 01 , respectively ) , but BKPC caused less cleavage and activation of caspase 3 than CCP alone ( P < 0 . 05 ) . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| In this report , we demonstrate that GzmB can initiate apoptosis in the absence of caspase 3 activity by directly cleaving DFF45 / ICAD to liberate activated DFF40 / CAD . ^^^ DFF45 / ICAD cleavage occurs less efficiently in cells that lack caspase 3 activity , suggesting that the caspases normally amplify the GzmB death signal . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| F15 tumor target cell , we show that ( a ) CTL from gzmA ( / ) or gzmB ( / ) mice similarly induced early proapoptotic features , such as phosphatidyl serine ( PS ) exposure on plasma membrane , Delta Psi ( m ) loss , and reactive oxygen radical generation , though with distinct kinetics ; ( b ) CTL from gzmA ( / ) but not from gzmB ( / ) mice activate caspase 3 and 9 ; ( c ) PS exposure induced by CTL from gzmA ( / ) or gzmB ( / ) mice is prevented , respectively , by caspase inhibitors or by reactive oxygen scavengers without interfering with target cell death ; and ( d ) all gzm induced apoptotic features analyzed depend critically on perf . ^^^ |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10144 and P42574 |
Pubmed |
SVM Score :0.0 |
| NA |
|