| Project/Area Number |
03044104
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KAMIRYO Tatsuyuki FACULTY OF INTEGRATED ARTS AND SCIENCES, HIROSHIMA UNIVERSITY, 総合科学部, 教授 (50025649)
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| Co-Investigator(Kenkyū-buntansha) |
WOLF HUBERT ドイツ, ボーフム大学・医学部, 教授
KUNAU WOLF-HUBERT MEDIZINISCHE FAKULTAT DER RUHR-UNIVERSITAT BOCHUM, F. R. G.
クナウ ウルフ・ヒューバ ボーフム大学, 医学部・ドイツ, 教授
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Zellweger Syndrome / Peroxisomes / Organelle Biogenesis / Yeast / PAS genes / ツェルベ-ガ-症 / ペルオキシソ-ム |
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| Research Abstract |
The primary defect arising from Zellweger syndrome is linked to impaired assembly of peroxisomes. The causes of the syndrome are thus far classified into 9 genetic complementation groups. For none of them, the function of the gene product has been understood. In this joint Research, yeast genes essential for the assembly of peroxisomes were isolated to study the process of the biogenesis of this organelle.
Sacchromyces cerevisiae mutants defective in peroxisome assembly were isolated that were able to grow on acetate but on oleic acid, and mislocated proxisomal matrix enzymes in the cytosol. There are 18 complementation groups of mutants (pas1-pas18). The PAS1 gene encoded a hydrophobic 117-kDa protein. The predicted sequence contained two putative ATP-binding sites and revealed a structural relationship to proteins involved in various cellular processes : control of cell cycle (Cdc48p), vesicle-mediated protein transport(Sec18p), and gene expression of HIV (TBP-1). The product of the PAS2 gene was the 10th member of the ubiquitin-conjugating protein family. The pas2 mutant cells accumulated the membranous structures that contained pas3p (see below). These structures could be the so-called ghosts of Zellweger fibroblasts. Pas3p, a 50.6-kDa protein encoded by the PAS3 gene, was supposed to be anchored in the peroxisomal membrane by its amino-terminus while the bulk of the molecule was exposed to cytosol.
The PAS1 homologue of a fatty-acid-assimilating yeast, Candida maltosa, was isolated. The cells lacking the wild-type alleles of PAS3 showed the same phenotype as the pas1 mutant in respect of the distribution of peroxisomal enzymes, and became sensitive to plumbagin, which is a potent propagator of reactive oxygen.
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