2003 Fiscal Year Final Research Report Summary
Structure and function of the ubiquitin ligase that recognizes N-linked oligosaccharides
| Project/Area Number |
14580635
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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 |
Structural biochemistry
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| Research Institution | The Tokyo Metropolitan Organization of Medical Science |
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Principal Investigator |
TAI Tadashi The Tokyo Metropolitan Organization of Medical Science, Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 参事研究員 (70112092)
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| Project Period (FY) |
2002 – 2003
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| Keywords | N-glycan / ubiquitin ligase / Fbx2 / proteasome / ERAD / Neuron |
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| Research Abstract |
N-glycosylation of proteins in the endoplasmic reticulum (ER) plays a key role in the protein quality control. Here we report that N-glycan serves as a degradation signal by the novel SCF^<Fbx2> ubiquitin-ligase complex in the cytosol. Fbx2,a F-box protein, binds specifically to proteins attached with N-linked high mannose type oligosaccharides, and subsequently contributes to ubiquitylation of N-glycosylated proteins. We identified pre-integrin β1 as one of the Fbx2 targets. This interaction was detected in the cytosol when the proteasome was inhibited. Furthermore, expression of Fbx2ΔF lacking the F-box domain essential for the formation of the SCF complex appreciably blocked degradation of typical substrates of ER-associated degradation, such as cystic fibrosis transmembrane conductance regulator mutant CFTRΔF508 and T-cell receptor a subunit, and Fbx2 suppressed aggregation of CFTRΔF508. These results indicate that SCF^<Fbx2> ubiquitylates N-glycosylated proteins, which are translocated from the ER to the cytosol by the quality control mechanism.
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