| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
In the previous studies, we have found that AICD has an ability to interact with tumor suppressor p53 in cells as examined by co-immunoprecipitation experiments, and also demonstrated that AICD enhances the transcriptional and pro-apoptotic functions of p53 (Ozaki, et. al., Biochem. Biophys. Res. Commun., 2006). These observations strongly suggest that AICD translocates from cytoplasm into cell nucleus, and acts as a co-activator for p53 to induce neuronal apoptotic cell death. Recently, it has been shown that Tip60 which contain an intrinsic acetyltransferase activity binds to p53 and enhances its transcriptional activity. Since AICD itself lacks the DNA-binding and transactivation abilities., it is likely that Tip60 might be involve al in AICD/p53-mediated apoptotic cell death lb address this issue, human neuroglioma-derived H4 cells were co-transfected with the expression plasmids for p53 and AICD together with or without the expression plasmid encoding Tip60. Consistent with the previous results, Tip60 was associated with MCD or p53 in cells. However Tip60 had undetectable effects on transcriptional activity of AICD/p53 complex under our experimental conditions. Thus, it is possible that Tip60 functions in a cell-type-dependent manner. Collectively, it is important to identify cellular protein (s) which might enhance the transcriptional and pro-apoptotic abilities of AICD/p63 complex. Lb address this issue, we have a plan to identify the binding partner (s) of AICD by yeast-based two-hybrid screening.
|
