The overall goal of the proposed research is to elucidate the cellular mechanisms that govern decisions of neuronal survival and death. The proposal outlines experiments that will dissect the mechanisms of FKHRL1-neuronal survival and death. The proposal outlines experiments that will dissect the mechanisms of FKHRL1-induced apoptosis in neurons.
The aims of the proposal are: 1) To determine the role of FKHRL1 in normal neuronal apoptosis by analyzing the effects of dominant negative isoforms on FH on apoptosis. 2) To determine the role of 14-3-3 proteins in the cytoplasmic localization of FKHRL1 by assaying for interactions between endogenous FN and 14-3-3 proteins and by analyzing the subcellular localization of mutant FH proteins that are unable to interact with 14-3-3 proteins. 3) To determine the molecular mechanisms for nuclear import and export of FH. Elucidating the involvement of FKHRL1 in neuronal apoptosis and understanding the mechanisms that regulate FKHRL1-induced apoptosis could lead to development of new therapeutics for neurodegenerative diseases or cancer-diseases characterized by abnormal regulation of growth, survival and apoptosis.
| Flavell, Steven W; Cowan, Christopher W; Kim, Tae-Kyung et al. (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008-12 |
| Sturla, Lisa-Marie; Cowan, Christopher W; Guenther, Lillian et al. (2005) A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer factor 2 in medulloblastoma cell death. Cancer Res 65:5683-9 |
