2012 Fiscal Year Final Research Report
A novel factor associated with TSC I/II may modulate neuronalsymptoms in TSC patients
| Project/Area Number |
22591219
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Osaka University |
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Principal Investigator |
KANEDA Mari 大阪大学, 医学系研究科, 講師 (70397644)
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| Project Period (FY) |
2010 – 2012
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| Keywords | mTOR / 結節性硬化症 / p40 / 神経皮膚症候群 / 精神神経疾患 / 腫瘍形成 / TSC1 / TSC2 |
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| Research Abstract |
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the hamartomas. Two genes, TSCI and TSCII, which encode hamartin and tuberin respectively, have been shown to be responsible for TSC. Hamartin and tuberin are associated with each other physically in vivo, and function in the same complex. We had identified that a 40 kD protein, p40, recognized by one monoclonal antibody, was significantly reduced in TSC patient cells. To compare the relation between clinical symptoms and loss of p40, the amount of p40 in the peripheral lymphocytes from TSC patients was related to the clinical symptoms, especially the neural symptoms of TSC such as convulsion and mental retardation. In this report, we showed the interaction of tuberin and/or hamartin and other proteins involved in the mTOR system with p40. To examine the association of p40 and tuberin or hamartin, knocked-down experiments and coprecipitation experiments were conducted. As a result, p40 was positively related to FKBP32 and FKBP12 and was directly associated with hamartin and indirectly with tuberin presumably via hamartin.
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