Alternative splicing of caspase-8 mRNA during differentiation of human leukocytes

Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we provide evidence that caspase-8 expression is subject to posttranscriptional regulation in human leukocytes. Resting peripheral blood lymphocytes preferentially use a distant splice donor site at the 3′-end of caspase-8 exon 8...

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Bibliographic Details
Main Authors: Eckhart, Leopold (Author) , Krammer, Peter H. (Author)
Format: Article (Journal)
Language:English
Published: 2001
In: Biochemical and biophysical research communications
Year: 2001, Volume: 289, Issue: 4, Pages: 777-781
ISSN:1090-2104
DOI:10.1006/bbrc.2001.6055
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1006/bbrc.2001.6055
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X01960553
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Author Notes:Leopold Eckhart, Michael Henry, Antonio M. Santos-Beneit, Ingo Schmitz, Andreas Krueger, Heinz Fischer, Jürgen Bach, Jozef Ban, Sabine Kirchhoff, Peter H. Krammer, Faustino Mollinedo, and Erwin Tschachler
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Summary:Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we provide evidence that caspase-8 expression is subject to posttranscriptional regulation in human leukocytes. Resting peripheral blood lymphocytes preferentially use a distant splice donor site at the 3′-end of caspase-8 exon 8 to generate mRNAs with a truncated open reading frame. When lymphocytes were activated, the expression of caspase-8 variants was shifted to caspase-8/a and b which lack the extension of exon 8. The opposite change of the splicing pattern was found in a neutrophil differentiation model. Promyelocytic HL-60 cells mainly expressed caspase-8 mRNAs with the normal exon 8, but the splicing pattern was changed to the distant exon 8 splice site during DMSO-induced differentiation of HL-60 cells. In spite of the presence of these novel mRNAs, the corresponding translation products were not detectable in either cell type. Our findings suggest that leukocyte differentiation and alternative splicing of caspase-8 pre-mRNA are inter-dependent processes.
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ISSN:1090-2104
DOI:10.1006/bbrc.2001.6055