Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets

Wang, Mingjun; Zhao, Xing‐Ming; Tan, Hao; Akutsu, Tatsuya; Whisstock, James C.; Song, Jiangning

doi:10.1093/bioinformatics/btt603

Cited by 69 publications

(73 citation statements)

References 65 publications

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“…Caspases cleave their substrates at specific tetrapeptides (canonical P4-P1 sites) with a highly conserved aspartate (D) at the P1 position, so we used several tools (Cascleave, Cascleave 2.0 and CaspDB) to predict the potential cleavage sites (Kumar et al, 2014; Song et al, 2010; Wang et al, 2014) (Table S2). The top two predicted caspase-3/7 cleavage sites (D100 and D433 obtained by Cascleave 2.0) are presented in Figure 5A.…”

Section: Resultsmentioning

confidence: 99%

B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation

Zhang

2017

Cell Reports

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SUMMARY Epstein-Barr virus (EBV) in tumor cells is predominately in latent phase but the virus can undergo lytic reactivation in response to various stimuli. However, the cellular factors that control latency and lytic replication are poorly defined. In this study, we demonstrated that a cellular factor, PIAS1, restricts EBV lytic replication. PIAS1-depletion significantly facilitated EBV reactivation, while PIAS1-reconstitution had the opposite effect. Remarkably, we found that various lytic triggers promote caspase-dependent cleavage of PIAS1 to antagonize PIAS1-mediated restriction, and that caspase inhibition suppresses EBV replication through blocking PIAS1 cleavage. We further demonstrated that a cleavage-resistant PIAS1 mutant suppresses EBV replication upon B cell receptor activation. Mechanistically, we demonstrated that PIAS1 acts as an inhibitor for transcription factors involved in lytic gene expression. Collectively, these results establish PIAS1 as a key regulator of EBV lytic replication and uncover a mechanism by which EBV exploits apoptotic caspases to antagonize PIAS1-mediated restriction.

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Section: Resultsmentioning

confidence: 99%

B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation

Zhang

2017

Cell Reports

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“…As an efficient machine learning algorithm, SVM has been widely used in protein bioinformatics [43–48]. In this work, the LIBSVM package (http://www.csie.ntu.edu.tw/~cjlin/libsvm/) was used as an implementation of SVM to train the classifiers [49].…”

Section: Methodsmentioning

confidence: 99%

Computational Identification of Protein Pupylation Sites by Using Profile-Based Composition of k-Spaced Amino Acid Pairs

Hasan

Zhou

et al. 2015

PLoS ONE

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Prokaryotic proteins are regulated by pupylation, a type of post-translational modification that contributes to cellular function in bacterial organisms. In pupylation process, the prokaryotic ubiquitin-like protein (Pup) tagging is functionally analogous to ubiquitination in order to tag target proteins for proteasomal degradation. To date, several experimental methods have been developed to identify pupylated proteins and their pupylation sites, but these experimental methods are generally laborious and costly. Therefore, computational methods that can accurately predict potential pupylation sites based on protein sequence information are highly desirable. In this paper, a novel predictor termed as pbPUP has been developed for accurate prediction of pupylation sites. In particular, a sophisticated sequence encoding scheme [i.e. the profile-based composition of k-spaced amino acid pairs (pbCKSAAP)] is used to represent the sequence patterns and evolutionary information of the sequence fragments surrounding pupylation sites. Then, a Support Vector Machine (SVM) classifier is trained using the pbCKSAAP encoding scheme. The final pbPUP predictor achieves an AUC value of 0.849 in10-fold cross-validation tests and outperforms other existing predictors on a comprehensive independent test dataset. The proposed method is anticipated to be a helpful computational resource for the prediction of pupylation sites. The web server and curated datasets in this study are freely available at http://protein.cau.edu.cn/pbPUP/.

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“…Using the web servers SitePrediciton and Cascleave, we identified a CASP3 and 7 cleavage site at amino acid 339 with >99% specificity in the GJA1 protein sequence (Fig. S1) (24,25). We used UV light exposure to activate CASP3 and 7 in an alternate non-ERSR-dependent manner in the hTERT-HM cells, and observed increased levels of active CASP3 and 7, corresponding to decreased levels of GJA1.…”

Section: Tm Induces Er Stress and Activates Apoptotic Casp3 Action Inmentioning

confidence: 99%

Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7–dependent

Kyathanahalli

Organ

Moreci

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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We previously identified myometrial caspase-3 (CASP3) as a potential regulator of uterine quiescence. We also determined that during pregnancy, the functional activation of uterine CASP3 is likely governed by an integrated endoplasmic reticulum stress response (ERSR) and is consequently limited by an increased unfolded protein response (UPR). The present study examined the functional relevance of uterine UPR-ERSR in maintaining myometrial quiescence and regulating the timing of parturition. In vitro analysis of the human uterine myocyte hTERT-HM cell line revealed that tunicamycin (TM)-induced ERSR modified uterine myocyte contractile responsiveness. Accordingly, alteration of in vivo uterine UPR-ERSR using a pregnant mouse model significantly modified gestational length. We determined that "normal" gestational activation of the ERSR-induced CASP3 and caspase 7 (CASP7) maintains uterine quiescence through previously unidentified proteolytic targeting of the gap junction protein, alpha 1 (GJA1); however, surprisingly, TM-induced uterine ERSR triggered an exaggerated UPR that eliminated uterine CASP3 and 7 tocolytic action precociously. These events allowed for a premature increase in myometrial GJA1 levels, elevated contractile responsiveness, and the onset of preterm labor. Importantly, a successful reversal of the magnified ERSR-induced preterm birth phenotype could be achieved by pretreatment with 4-phenylbutrate, a chaperone protein mimic.endoplasmic reticulum stress | caspase-3 and -7 | unfolded protein response | preterm labor | uterus

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Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets

Abstract: http://www.structbioinfor.org/cascleave2/.

Cited by 69 publications

References 65 publications

B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation

B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation

Computational Identification of Protein Pupylation Sites by Using Profile-Based Composition of k-Spaced Amino Acid Pairs

Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7–dependent

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