| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
The highly conserved RCAN family of proteins regulates the serine/threonine protein phosphatase calcineurin, which is required for the expression of genes involved in Ca^<2+->dependent processes such as the control of memory, apoptosis, T cell activation, cell cycle and cardiac muscle growth and differentiation. However, RCANs regulate calcineurin through two paradoxical actions: they act as feedback inhibitors of calcineurin, whereas their phosphorylation stimulates calcineurin. Here we showed that phosphorylation of RCAN triggers degradation through the SCF ubiquitin ligase complex in yeast and in human. Degradation of phosphorylated RCAN is required to mitigate inhibition of calcineurin by RCAN and results in activation of calcineurin in response to changes in Ca^<2+> concentration. Such phosphorylayion was counteracted by dephosphorylation of RCAN, which was promoted by Ca^<2+->stimulated calcineurin. These results provide insight into the mechanism involved in maintaining proper responses to Ca^<2+> signals.
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