| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Research Abstract |
In addition to G-protein coupled receptors, there exist receptor-independent regulators for heterotrimeric G-proteins which provide alternative signal input that may be involved in the adaptation process of cells to various stresses. As a part of an effort to identify such entities in cardiovascular diseases, we used a functional screen to identify receptor-independent activators of G-protein signaling (AGS) in the hypertrophied mouse heart by transverse aortic constriction. We identified three MITF/TFE transcription factors, TFE3 as novel AGS proteins for Gα16. TFE3 induced translocation of Gα16 to the nucleus. Interestingly, the accumulation of TFE3/Gα16 in the nucleus induced the expression of claudin 14, which was a key component of membrane structure in cardiomyocytes.TFE3 transcription factor is a new AGS for Gα16, that appears to generate a TEF3/Gα16 complex in the nucleus that drives the transcription of claudin 14. These findings suggest the existence of a novel mechanism of transcriptional regulation under pressure overload stress via the relocalization/activation of Gα subunit with specific AGS proteins.
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