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dc.contributor.authorSong, QZ
dc.contributor.authorBurrows, SR
dc.contributor.authorSmith, G
dc.contributor.authorLeesMiller, SP
dc.contributor.authorKumar, S
dc.contributor.authorChan, DW
dc.contributor.authorTrapani, JA
dc.contributor.authorAlnemri, E
dc.contributor.authorLitwack, G
dc.contributor.authorLu, H
dc.contributor.authorMoss, DJ
dc.contributor.authorJackson, S
dc.contributor.authorLavin, MF
dc.date.accessioned2020-12-22T03:19:27Z
dc.date.available2020-12-22T03:19:27Z
dc.date.issued1996-08-01
dc.identifier.citationSong, Q. Z., Burrows, S. R., Smith, G., LeesMiller, S. P., Kumar, S., Chan, D. W., Trapani, J. A., Alnemri, E., Litwack, G., Lu, H., Moss, D. J., Jackson, S. & Lavin, M. F. (1996). Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing. JOURNAL OF EXPERIMENTAL MEDICINE, 184 (2), pp.619-626. https://doi.org/10.1084/jem.184.2.619.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/257827
dc.description.abstractCytotoxic T cells (CTL) represent the major defense mechanism against the spread of virus infection. It is believed that the pore-forming protein, perforin, facilitates the entry of a series of serine proteases (particularly granzyme B) into the target cell which ultimately leads to DNA fragmentation and apoptosis. We demonstrate here that during CTL-mediated cytolysis the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an enzyme implicated in the repair of double strand breaks in DNA, is specifically cleaved by an interleukin (IL)-1 beta-converting enzyme (ICE)-like protease. A serine protease inhibitor, 3,4-dichloroisocoumarin (DCl), which is known to block granzyme B activity, inhibited CTL-induced apoptosis and prevented the degradation of DNA-PKcs in cells but failed to prevent the degradation of purified DNA-PKcs by CTL extracts. However, Tyr-Val-Ala-Asp-CH2Cl (YVAD-CMK) and other cysteine protease inhibitors prevented the degradation of purified DNA-PKcs by CTL extracts. 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, CPP32. Sequence analysis revealed that the cleavage site in DNA-PKcs during CTL killing was the same as that when this substrate was exposed to CPP32. This study demonstrates for the first time that the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE-like protease.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleInterleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing
dc.typeJournal Article
dc.identifier.doi10.1084/jem.184.2.619
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume184
melbourne.source.issue2
melbourne.source.pages619-626
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1179889
melbourne.contributor.authorTrapani, Joseph
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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