Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I

Shigehiko Tamura, Kanji Okumoto, Ryusuke Toyama, Nobuyuki Shimozawa, Toshiro Tsukamoto, Yasuyuki Suzuki, Takashi Osumi, Naomi Kondo, Yukio Fujiki

研究成果: ジャーナルへの寄稿記事

84 引用 (Scopus)

抄録

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 → Pro and a deletion of the sequence from Gly- 634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.

元の言語英語
ページ(範囲)4350-4355
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
95
発行部数8
DOI
出版物ステータス出版済み - 4 14 1998

Fingerprint

Zellweger Syndrome
Peroxisomes
Cricetulus
Peroxisomal Disorders
Ovary
Complementary DNA
Fibroblasts
Transformed Cell Line
Mutation
Sequence Deletion
Missense Mutation
Point Mutation
Adenosine Triphosphatases
Proteins
Amino Acids
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • General

これを引用

Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I. / Tamura, Shigehiko; Okumoto, Kanji; Toyama, Ryusuke; Shimozawa, Nobuyuki; Tsukamoto, Toshiro; Suzuki, Yasuyuki; Osumi, Takashi; Kondo, Naomi; Fujiki, Yukio.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 95, 番号 8, 14.04.1998, p. 4350-4355.

研究成果: ジャーナルへの寄稿記事

Tamura, Shigehiko ; Okumoto, Kanji ; Toyama, Ryusuke ; Shimozawa, Nobuyuki ; Tsukamoto, Toshiro ; Suzuki, Yasuyuki ; Osumi, Takashi ; Kondo, Naomi ; Fujiki, Yukio. / Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I. :: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 巻 95, 番号 8. pp. 4350-4355.
@article{6020bf12d09f44f0a1bbe1ccf44b02e8,
title = "Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I",
abstract = "The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 → Pro and a deletion of the sequence from Gly- 634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.",
author = "Shigehiko Tamura and Kanji Okumoto and Ryusuke Toyama and Nobuyuki Shimozawa and Toshiro Tsukamoto and Yasuyuki Suzuki and Takashi Osumi and Naomi Kondo and Yukio Fujiki",
year = "1998",
month = "4",
day = "14",
doi = "10.1073/pnas.95.8.4350",
language = "English",
volume = "95",
pages = "4350--4355",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I

AU - Tamura, Shigehiko

AU - Okumoto, Kanji

AU - Toyama, Ryusuke

AU - Shimozawa, Nobuyuki

AU - Tsukamoto, Toshiro

AU - Suzuki, Yasuyuki

AU - Osumi, Takashi

AU - Kondo, Naomi

AU - Fujiki, Yukio

PY - 1998/4/14

Y1 - 1998/4/14

N2 - The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 → Pro and a deletion of the sequence from Gly- 634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.

AB - The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 → Pro and a deletion of the sequence from Gly- 634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.

UR - http://www.scopus.com/inward/record.url?scp=0032515992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032515992&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.8.4350

DO - 10.1073/pnas.95.8.4350

M3 - Article

C2 - 9539740

AN - SCOPUS:0032515992

VL - 95

SP - 4350

EP - 4355

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -