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Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo
Open accessAbstract
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of activated cytotoxic lymphocytes. In this report, we show that cytotoxic lymphocytes derived from DPPI−/− mice contain normal amounts of granzymes A and B, but these molecules retain their prodipeptide domains and are inactive. Cytotoxic assays with DPPI−/− effector cells reveal severe defects in the induction of target cell apoptosis (as measured by [125 I]UdR release) at both early and late time points; this defect is comparable to that detected in perforin−/− or granzyme A−/− × B−/− cytotoxic lymphocytes. DPPI therefore plays an essential role in the in vivo processing and activation of granzymes A and B, which are required for cytotoxic lymphocyte granule-mediated apoptosis.
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Cited by
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Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., & Turk, D. (2012) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2011.10.002 · Cited by 1,377
Perforin and granzymes: function, dysfunction and human pathology
Voskoboinik, I., Whisstock, J. C., & Trapani, J. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3839 · Cited by 1,327
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Voskoboinik, I., Smyth, M. J., & Trapani, J. A. (2006) · Nature reviews. Immunology · doi:10.1038/nri1983 · Cited by 592
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Shree, T., Olson, O. C., Elie, B. T., Kester, J. C., Garfall, A. L., Simpson, K., Bell-McGuinn, K. M., Zabor, E. C., Brogi, E., & Joyce, J. A. (2011) · Genes & Development · doi:10.1101/gad.180331.111 · Cited by 541
Metadata
- Authors
- Pham, C. T. N., & Ley, T. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-07-20
- Volume
- 96
- Issue
- 15
- Pages
- 8627-8632
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2170872843
- Cited by
- 397
- References
- 0
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
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- Pham, C. T. N., & Ley, T. J. (1999). Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.15.8627
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
