CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases

M A Cahill, M E Peter, F C Kischkel, A M Chinnaiyan, V M Dixit, P H Krammer, A Nordheim

Research output: Contribution to journalArticle

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Abstract

Triggering of CD95 (APO-1/Fas) on different T- and B-cell lines resulted in the induction of a number of kinases (35 kDa, 38 kDa, 46 kDa and 54 kDa) that phosphorylate c-Jun and to a lesser extent Histone H1. Activation of these kinases was independent of protein biosynthesis and preceded apoptotic DNA degradation. The kinase activation pattern was specific for CD95 triggering since a variety of physical or chemical inducers of T- and B-cell apoptosis activated different kinases. The kinase activities at 46 and 54 kDa contained members of the stress-activated family of protein kinases (JNK/SAPK). Activation of the CD95-specific set of kinases was prevented by treating cells with the ICE-inhibiting peptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) or by overexpression of the cow pox virus serpin CrmA. However, despite inhibition of ICE-like proteases the death signal was readily initiated at the cell membrane since a CD95 death-inducing signaling complex (DISC) was formed. Thus, our results demonstrate that ICE-like proteases in the CD95 pathway function downstream of the DISC but upstream of SAP kinases.

Original languageEnglish
Pages (from-to)2087-96
Number of pages10
JournalOncogene
Volume13
Issue number10
Publication statusPublished - 21 Nov 1996

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Caspase 1
Phosphotransferases
Death Domain Receptor Signaling Adaptor Proteins
B-Lymphocytes
Cowpox virus
Serpins
Protein Biosynthesis
DNA Fragmentation
Histones
Protein Kinases
Cell Membrane
Apoptosis
Cell Line
Peptides

Cite this

Cahill, M. A., Peter, M. E., Kischkel, F. C., Chinnaiyan, A. M., Dixit, V. M., Krammer, P. H., & Nordheim, A. (1996). CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. Oncogene, 13(10), 2087-96.
Cahill, M A ; Peter, M E ; Kischkel, F C ; Chinnaiyan, A M ; Dixit, V M ; Krammer, P H ; Nordheim, A. / CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. In: Oncogene. 1996 ; Vol. 13, No. 10. pp. 2087-96.
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Cahill, MA, Peter, ME, Kischkel, FC, Chinnaiyan, AM, Dixit, VM, Krammer, PH & Nordheim, A 1996, 'CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases', Oncogene, vol. 13, no. 10, pp. 2087-96.

CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. / Cahill, M A; Peter, M E; Kischkel, F C; Chinnaiyan, A M; Dixit, V M; Krammer, P H; Nordheim, A.

In: Oncogene, Vol. 13, No. 10, 21.11.1996, p. 2087-96.

Research output: Contribution to journalArticle

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T1 - CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases

AU - Cahill, M A

AU - Peter, M E

AU - Kischkel, F C

AU - Chinnaiyan, A M

AU - Dixit, V M

AU - Krammer, P H

AU - Nordheim, A

PY - 1996/11/21

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N2 - Triggering of CD95 (APO-1/Fas) on different T- and B-cell lines resulted in the induction of a number of kinases (35 kDa, 38 kDa, 46 kDa and 54 kDa) that phosphorylate c-Jun and to a lesser extent Histone H1. Activation of these kinases was independent of protein biosynthesis and preceded apoptotic DNA degradation. The kinase activation pattern was specific for CD95 triggering since a variety of physical or chemical inducers of T- and B-cell apoptosis activated different kinases. The kinase activities at 46 and 54 kDa contained members of the stress-activated family of protein kinases (JNK/SAPK). Activation of the CD95-specific set of kinases was prevented by treating cells with the ICE-inhibiting peptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) or by overexpression of the cow pox virus serpin CrmA. However, despite inhibition of ICE-like proteases the death signal was readily initiated at the cell membrane since a CD95 death-inducing signaling complex (DISC) was formed. Thus, our results demonstrate that ICE-like proteases in the CD95 pathway function downstream of the DISC but upstream of SAP kinases.

AB - Triggering of CD95 (APO-1/Fas) on different T- and B-cell lines resulted in the induction of a number of kinases (35 kDa, 38 kDa, 46 kDa and 54 kDa) that phosphorylate c-Jun and to a lesser extent Histone H1. Activation of these kinases was independent of protein biosynthesis and preceded apoptotic DNA degradation. The kinase activation pattern was specific for CD95 triggering since a variety of physical or chemical inducers of T- and B-cell apoptosis activated different kinases. The kinase activities at 46 and 54 kDa contained members of the stress-activated family of protein kinases (JNK/SAPK). Activation of the CD95-specific set of kinases was prevented by treating cells with the ICE-inhibiting peptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) or by overexpression of the cow pox virus serpin CrmA. However, despite inhibition of ICE-like proteases the death signal was readily initiated at the cell membrane since a CD95 death-inducing signaling complex (DISC) was formed. Thus, our results demonstrate that ICE-like proteases in the CD95 pathway function downstream of the DISC but upstream of SAP kinases.

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KW - Antigens, CD95

KW - Apoptosis

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Caspase 1

KW - Cell Line

KW - Cysteine Endopeptidases

KW - DNA

KW - Enzyme Activation

KW - Enzyme Inhibitors

KW - Humans

KW - Lymphoma, B-Cell

KW - Lymphoma, T-Cell

KW - Mice

KW - Signal Transduction

KW - Staurosporine

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

UR - http://www.ncbi.nlm.nih.gov/pubmed/8950975

M3 - Article

C2 - 8950975

VL - 13

SP - 2087

EP - 2096

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 10

ER -

Cahill MA, Peter ME, Kischkel FC, Chinnaiyan AM, Dixit VM, Krammer PH et al. CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. Oncogene. 1996 Nov 21;13(10):2087-96.