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

作者：Hellwig Christian T; Ludwig Galezowska Agnieszka H; Concannon Caoimhin G; Litchfield David W; Prehn Jochen H M; Rehm Markus^*

来源：Journal of Cell Science, 2010, 123(9): 1401-1406.

DOI：10.1242/jcs.061143

• Apoptosis
• Tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL)
• Protein kinase CK2
• Bid
• Caspase-8
• Forster resonance energy transfer (FRET)

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-1-(beta-D-ribofuranosyl-1)-benzimidazole (DRB) or by overexpression of a dominant-negative CK2 alpha 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.

• 出版日期2010-5-1