| Project/Area Number |
17591234
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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 |
Psychiatric science
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| Research Institution | NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY |
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Principal Investigator |
YAMADA Misa NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, DIVISION OF PSYCHOGERIATRICS, RISEARCHER, 精神保健研究所・老人精神保健部, 研究員 (10384182)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Mitsuhiko NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, DIVISION OF PSYCHOGERIATRICS, DIRECTOR, 精神保健研究所・老人精神保健部, 部長 (60240040)
SAITO Toshikazu SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (50128518)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ANTIDEPRESSANT / ECT / r TMS / DIFFERENTIAL CLONING / ENDOPLASMIC RETICULUM / プロテアソーム / ユビキチン |
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| Research Abstract |
We have previously performed EST analysis and identified some common biological changes induced after chronic antidepressant treatment as antidepressant related genes/ESTs : ADRG#1-707. In the present study, we focus on ADRG#34. The expressin of ADRG#34 was induced after chronic treatment with antidepressant, electro-convulsive treatment or repetitive transcranial magnetic stimulation in rat brain. The immunohistochemistry showed that ADRG#34 was expressed in endoplasmic reticulum but not in golgi apparatus in HEK 293 cells. Then the functions of human homologue of ADREG#34 (hADRG#34) which had RING-H2 finger motif were determined. RING finger proteins have been shown to participate in the ubiquitin-proteasome degradation system by activating E2-dependent ubiquitination. In line with this premise, we demonstrated that hADRG#34 has in vitro ubiquitination activity in the presence of ubiquitin activating enzyme (El), UbcH5b (E2), hADRG#34, ubiquitin (Ub), b-lactoglobulin as substrate, ubiquitin, and reaction buffer containing ATP. Indeed, the ubiquitinqted products immunoprecipitated by hADRG#34 were increased after addition of MG-132, proteasome inhibitor in hADRG#34 and ubiquitin co-transfected HEK293 cells. Our results indicated that ADRG#34 has E3 ubiquitin ligase activity both in vitro and in vivo.
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