| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Research Abstract |
The TEAD family of transcription factors is a key factor in regulating cell proliferation and organ size via Hippo signaling pathway. Recent studies have revealed that a missense mutation in human TEAD1 is genetically linked to Sveinsson's chorioretinal atrophy (SCRA). To clarify the molecular mechanisms, we established a tetracycline-induclibe cell line which can express the mutant protein by adding tetracycline. The induction of missense mutation reduced the expression of a CTGF promoter-drived reporter gene. In fact, the mutation also abolished the transcriptional activity of the reporter gene under the co-expression of YAP or TAZ, suggesting the mutant act as a dominant-negative form on the transcriptional activity of Tead1. These results suggest that the mutant Tead1 repress the expression of Tead1 target genes and the proliferation of retinal pigment epithelial cells.
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