| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
We found an ubiquitin ligase, SCF^<Fbs1>, which recognizes N-glycans in glycoproteins. When the endoplasmic reticulum (ER)-resident newly synthesized proteins are not folded properly, they are degraded through the ER-associated degradation (ERAD) pathway. The analysis of substrates of SCF^<Fbs1> has shown that SCF^<Fbs1> is involved in the ERAD pathway. Other than Fbs1, at least four F-box proteins (Fbs2, Fbg3-5) that show high homology in the substrate-binding domain (SBD) have been reported. However, it remains to be established whether Fbg3,4, and 5 proteins bind specific N-glycans and what are their substrates. In this study, we have tried to elucidate the roles of Fbs1 homologs in vivo.
Although the amino acid identity in SBD between Fbs2 and Fbg3 proteins and between Fbg4 and Fbg5 proteins display more than 60%, only Fbs2 and Fbg5 have the ability to bind N-glycans as well as Fbs1. We have identified the proteins that interact to F-box proteins by using TOF-MS.
We show that the in vivo majority of Fbs1 is present as Fbs1-Skp1 heterodimers but not SCF complex. Moreover, Fbs1 prevented the aggregation of the glycoproteins in vivo and in vitro. Fbs1 is present abundantly in the nervous system, and Fbs1 assists clearance of aberrant glycoproteins in neuronal cells by suppressing aggregates formation, independent of ubiquitin ligase activity, and thus functions as a unique chaperone for those proteins.
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