Type

Journal Article

Authors

Markus Rehm
Jochen H M Prehn
David W Litchfield
Caoimhín G Concannon
Agnieszka H Ludwig-Galezowska
Christian T Hellwig

Subjects

Biochemistry

Topics
bh3 interacting domain death agonist protein time factors metabolism humans protein structure tertiary pharmacology casein kinase ii protein kinase inhibitors fluorescence resonance energy transfer kinetics tnf related apoptosis inducing ligand chemistry drug effects signal transduction apoptosis caspase 8 antagonists inhibitors hela cells substrate specificity enzyme activation

Activity of protein kinase CK2 uncouples Bid cleavage from caspase-8 activation. (2010)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

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

Experts in our system

1
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55
 
2
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
3
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
4
Christian T Hellwig
Royal College of Surgeons in Ireland
Total Publications: 11