Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Outline of Final Research Achievements |
We investigated the cellular mechanism underlying the degradation of heme oxygenase-1 (HO-1). 1) The turnover of HO-1 induced in HEK293 was significantly attenuated by proteasome inhibitors, suggesting the involvement of a proteasome-mediated pathway. 2) High molecular weight ubiquitin conjugates were co-immunoprecipitated with HO-1 from HEK293 after proteasome inhibition. 3) HO-1 ubiquitination in HEK293 cells was enhanced by zinc chloride, but suppressed with a zinc chelator, suggesting the involvement of a RING-E3 ligase in this process. 4) We identified TRC8 as the E3 ligase responsible for HO ubiquitination and degradation using mass spectrometry, yeast two-hybrid assay and cDNA array.
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