Project Details
Description
DESCRIPTION: (Adapted from the Investigator's abstract): Activation-induced
cell death (AICD) is one of the fundamental mechanisms maintaining immune
tolerance and lymphocyte homeostasis. AICD often proceeds via signals generated
by the interaction between Fas (CD95/APO-1)/Fas ligand (FasL/CD95L), which
elicits the activation of a cascade of caspases responsible for executing the
apoptosis process in a transcription-independent manner. Thus, the expression
of Fas and FasL is on of the final checkpoints determining the fate of
activated T lymphocytes. While extensive studies have been conducted on
Fas/FasL-induced execution machinery, our research has investigated on the
molecular mechanisms regulating the expression of Fas and FasL. Our previous
studies have demonstrated that activation of T-cell hybridomas leads to AICD, a
process completely dependent on Fas and FasL. Earlier, we reported a crucial
role of proto-oncoprotein c-Myc in activation-induced apoptosis; we have
recently determined that the effect of c-Myc is exerted through regulating FasL
expression. Moreover, Fas L expression requires both PKC activation and Ca++
mobilization, appears to be restricted to G1/M phase of the cell cycle, and is
regulated solely by the activity of PKC, probably by regulating TDAG51 and p53.
Therefore, the expression of Fas and FasL is strictly controlled by distinct
molecular pathways. The goal of this application is to characterize molecular
mechanisms regulating Fas/FasL expression. The experiments will examine cell
cycle status in the control of FasL expression, with particular emphasis on the
role of c-Myc and cdc5A by sense and anti-sense transfections. In addition,
they will investigate the process of TCR-mediated PKC activation and how PKC
activity is exerted through modulating the function of TDAG51 and p53 in the
regulation of Fas expression. These studies will shed new light on the
understanding of the molecular mechanisms by which the immune system is
regulated through apoptosis. Since Fas/FasL-mediated cell death has been
implicated in tumor immunity, cancer development, neutronal degeneration, and
aging, the elucidation of the mechanisms regulating Fas/FasL expression will
enable better management and prognosis of these diseases.
Status | Finished |
---|---|
Effective start/end date | 8/1/99 → 6/30/05 |
Funding
- National Institute of Allergy and Infectious Diseases: $197,482.00
- National Institute of Allergy and Infectious Diseases: $34,063.00
- National Institute of Allergy and Infectious Diseases: $231,874.00
- National Institute of Allergy and Infectious Diseases: $224,803.00
- National Institute of Allergy and Infectious Diseases: $246,441.00
ASJC
- Molecular Biology
- Cell Biology
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.