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HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation

Infection of T cells with HIV-1 induces apoptosis and modulates apoptosis regulatory molecules. Similar effects occur following treatment of cells with individual HIV-1 encoded proteins. While HIV-1 protease is known to be cytotoxic, little is known of its effect on apoptosis and apoptosis regulator...

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Bibliographische Detailangaben
Hauptverfasser: Nie, Zelin (VerfasserIn) , Krammer, Peter H. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 29 October 2002
In: Cell death and differentiation
Year: 2002, Jahrgang: 9, Heft: 11, Pages: 1172-1184
ISSN:1476-5403
DOI:10.1038/sj.cdd.4401094
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.cdd.4401094
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/4401094
Volltext
Verfasserangaben:Z. Nie, B.N. Phenix, J.J. Lum, A. Alam, D.H. Lynch, B. Beckett, P.H. Krammer, R.P. Sekaly and A.D. Badley
Beschreibung
Zusammenfassung:Infection of T cells with HIV-1 induces apoptosis and modulates apoptosis regulatory molecules. Similar effects occur following treatment of cells with individual HIV-1 encoded proteins. While HIV-1 protease is known to be cytotoxic, little is known of its effect on apoptosis and apoptosis regulatory molecules. The ability of HIV-1 protease to kill cells, coupled with the degenerate substrate specificity of HIV-1 protease, suggests that HIV-1 protease may activate cellular factor(s) which, in turn, induce apoptosis. We demonstrate that HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, cleavage of DFF and PARP and, eventually, to nuclear condensation and DNA fragmentation that are characteristic of apoptosis. The effect of HIV-1 protease is not seen in T cell extracts which have undetectable levels of procaspase 8, indicating a specificity and requirement for procaspase 8.
Beschreibung:Gesehen am 14.04.2021
Beschreibung:Online Resource
ISSN:1476-5403
DOI:10.1038/sj.cdd.4401094

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