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Activity of protein kinase CK2 uncouples Bid cleavage from caspase-8 activation.

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posted on 22.11.2019 by Christian T. Hellwig, Agnieszka H. Ludwig-Galezowska, Caoimhín G. Concannon, David W. Litchfield, Jochen H M Prehn, Markus Rehm

In the present study, we quantitatively analysed the interface between apoptosis initiation and execution by determining caspase-8 activation, Bid cleavage and mitochondrial engagement (onset of mitochondrial depolarisation) in individual HeLa cervical cancer cells following exposure to tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Employing resonance-energy-transfer probes containing either the caspase-8 recognition site IETD or full-length Bid, we observed a significant delay between the times of caspase-8 activation and Bid cleavage, suggesting the existence of control steps separating these two processes. Subsequent analyses suggested that the divergence of caspase-8 activation and Bid cleavage are critically controlled by kinase signalling: inhibiting protein kinase CK2 by using 5,6-dichloro-l-(beta-D-ribofuranosyl-1)-benzimidazole (DRB) or by overexpression of a dominant-negative CK2alpha catalytic subunit largely eliminated the lag time between caspase-8 activation and Bid cleavage. We conclude that caspase-8 activation and Bid cleavage are temporally uncoupled events, providing transient tolerance to caspase-8 activities.

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Published Citation

Hellwig CT, Ludwig-Galezowska AH, Concannon CG, Litchfield DW, Prehn JHM, Rehm M. Activity of protein kinase CK2 uncouples Bid cleavage from caspase-8 activation. Journal of Cell Science. 2010;23(9):1401-6 epub.

Publication Date

01/05/2010

Publisher

Company of Biologists

PubMed ID

20356928

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