2012 Fiscal Year Final Research Report
Physiological roles ofER-associated degradation in osteogenesis and chondrogenesis.
| Project/Area Number |
23790340
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | タンパク質分解 / 骨・軟骨形成 |
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| Research Abstract |
BBF2H7 and OASIS, ER-resident transmembrane proteins, have beenidentified as novel ER stress transducers that have roles in chondrogenesis and osteogenesis. BBF2H7 and OASIS are notably unstable proteins that are easily degraded via the ubiquitin-proteasome pathway under normal conditions. ER stress conditions enhanced the stability of BBF2H7 and OASIS, and promoted transcription of their target genes. HMG-CoA reductase degradation 1 (HRD1), an ER-resident E3 ubiquitin ligase, ubiquitinated BBF2H7 and OASIS under normal conditions, whereas ER stress conditions dissociated the interaction between HRD1 and BBF2H7 or OASIS. The stabilizationof OASIS in Hrd1-/- cells enhanced the expression of collagen fibers during osteoblast differentiation, whereas a knockdown of OASIS in Hrd1-/- cells suppressed the production of collagen fibers. These findings suggest that ER stress stabilizes OASIS family membersand this is a novel molecular mechanism for the activation of ER stress transducers.
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[Journal Article] Activation of OASIS family, ER stress transducers, is dependent on its stabilization.2012
Author(s)
Kondo S,Hino S-I, Saito A, Kanemoto S, Kawasaki N, Asada R, Izumi S, Iwamoto H, Oki M, Miyagi H, Kaneko M, Nomura Y, Urano F and Imaizumi K
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Journal Title
Cell death and differentiation
Volume: 19
Pages: 1939-1949
DOI
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