This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.JTV/p38 has been suggested as the Autosomal Recessive Juvenile Parkinsonism disease-causing target. JTV/p38, by itself, is incapable of binding to DNA, suggesting that it must interact with other DNA-binding factors to regulate transcription. Thus, to identify JTV/p38's direct targets, it is crucial to find its partners though high-throughput protein-protein interaction screening. ChIP-on-chip is the only way to look for direct targets of JTV/p38. However, we have found approximately 280 genes whose expression levels were changed as a result of over-expression of JTV/p38 by conventional expression microarray experiments. Therefore, it will be difficult to separate direct JTV/p38 targets from secondary effects without knowing JTV/p38's binding partner(s). We will use the flow cytometric two hybrid screening system developed in the NFCR to screen for JTV/p38 binding partners directly in mammalian cells. The results from the screening of JTV/p38 interaction partners will allow us to identify critical disease regulation pathways.
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