Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
|
Research Abstract |
Shh signaling pathway is conserved among animals and has pivotal roles in embryonic development, in the maintenance of adult stem cells, and in cancer. FKBP38 has been shown to act in a cell-autonomous manner to prevent inappropriate activation of the Shh pathway. It has remained unclear, however, how FKBP38 suppresses Shh signaling. With the use of a proteomics approach to the discovery of proteins that regulate Shh signaling in association with FKBP38, we have now identified ANKMY2 as a molecule that interacts with FKBP38. Depletion or overexpression of ANKMY2 resulted in down- and up-regulation of Shh signaling, respectively, in mouse embryonic fibroblasts. Furthermore, combined depletion of both FKBP38 and ANKMY2 attenuated Shh signaling in these cells, suggesting that ANKMY2 acts downstream of FKBP38 to activate the Shh signaling pathway. Our findings thus indicate that the FKBP38-ANKMY2 axis plays a key role in regulation of Shh signaling in vivo.
|