Biochemistry Publications

Activity of Protein Kinase CK2 Uncouples Bid Cleavage from Caspase-8 Activation

Document Type

Article

Publication Date

5-2010

Journal

Journal of Cell Science

Volume

123

Issue

9

First Page

1401

Last Page

1406

URL with Digital Object Identifier

http://dx.doi.org/10.1242/jcs.061143

Abstract

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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