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RGD containing peptides as novel activators of caspase 3: studies of caspase enzymology and function in T cell apoptosis

Reference	C11066
Principal Investigator / Supervisor	Professor Janet Lord
Co-Investigators / Co-Supervisors	Professor Michael Salmon
Institution	University of Birmingham
Department	Medical Sciences - Medicine
Funding type	Research
Value (£)	159,191
Status	Completed
Type	Research Grant
Start date	01/02/1999
End date	01/08/2002
Duration	42 months

Abstract

Synthetic peptides containing the Arg-Gly-Asp (RGD) motif have been used as inhibitors of integrin-ligand interactions to examine the biological role of these molecules in cell adhesion, migration, differentiation and death. We have recently shown that this concept is flawed, because RGD peptides enter cells and appear to directly activate caspase 3 leading to apoptosis. This is the first description of a specific caspase activating peptide. The presence in caspase 3 of an RGD motif at the enzymatically active site, and a DDM counter-receptor at the cleavage site, suggests a direct molecular mechanism for caspase 3 auto-cleavage. We aim to investigate the role of caspase RGD motifs in caspase activation. In addition, the HIV- 1 Tat protein induces T cell apoptosis, and contains an RGD motif. We will test whether this operates by direct caspase activation.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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