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Tumour necrosis factor-alpha signalling mechanisms employed in cell life and death

Reference	C12918
Principal Investigator / Supervisor	Professor David MacEwan
Co-Investigators / Co-Supervisors
Institution	University of Aberdeen
Department	Biomedical Sciences
Funding type	Research
Value (£)	163,740
Status	Completed
Type	Research Grant
Start date	01/10/2000
End date	01/10/2003
Duration	36 months

Abstract

We have uncovered an interesting haematopoietic human cell model (TF-1 cells) in which the cells will respond to tumour necrosis factor-alpha (TNF) by undergoing either apoptotic cell death or proliferation, dependent on the mitotic activity of the cells. This life or death control is directed by TNF receptor subtype expression. This study will investigate the differential signalling mechanisms employed by the two TNF receptor subtypes (p55TNFR and p75TNFR) to command the cells to proliferate or die. Our hypothesis is that the overexpression of the p75TNFR (conditions which lead to TNF-induced cell death) signals for significant activation of stress-activated protein kinase (SAPK) pathways; whereas lowered expression of p75TNFR (when cells proliferate in response to TNF) will result in lesser SAPK activation but greater mitogen-activated protein kinase (MAPK) pathways activation. We will confirm the differential effects of these kinase pathways on down-stream transcriptional elements such as c-Jun and Elk-1, or NF-kB (controlled by the NIK/IKK kinase pathway). The net effects of these opposing signalling pathways may be decisive in predetermining the fate of TF-1 cells, and will better our understanding of the TNF signalling for proliferation or cell death within the same cell type.

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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