| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Research Abstract |
Thalidomide is known for its teratogenicity, however it is also recognised as a clinically effective drug for the treatment of myeloma. Although the molecular targets of thalidomide were a long-standing question, we recently identified protein cereblon (CRBN) as a primary target of thalidomide induced teratogenicity. Our data suggest that thalidomide inhibits the E3 ubiquitin ligase function of CRBN but the detail mechanism is still largely unknown. In this study, I have analysed the inhibitory mechanism of the CRBN function by thalidomide using biochemical approaches. My data suggest that thalidomide binding to CRBN alters CRBN-E3-ubiquitin-ligase substrate specificity. Thus, thalidomide-bound CRBN may no longer recognise original substrates resulting in the inhibition of its E3-ubiquitin-ligase function.
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