Disease relevance of PEX1

• These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders [1].

High impact information on PEX1

• Pex14p, an S. cerevisiae peroxin, is attached to the outer face of the peroxisomal membrane and is a component of the protein import machinery [2].
• Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders [3].
• These data demonstrate an important role for PEX1 in peroxisome biogenesis and suggest that mutations in this gene are the most common cause of the PBDs [3].
• Expression of PEX1 rescued the cells from the biogenesis defect in human fibroblasts of complementation group 1 (CG1), the largest PBD complementation group [4].
• Human PEX1 has been identified by computer-based 'homology probing' using the ScPex1p sequence to screen databases of expressed sequence tags (dbEST) for human cDNA clones [4].

Biological context of PEX1

• In contrast with the other two genes studied, PEX1 is up-regulated in anaerobiosis [5].
• Pex17p of Saccharomyces cerevisiae is a novel peroxin and component of the peroxisomal protein translocation machinery [6].
• NVL was isolated by degenerate PCR using oligonucleotides corresponding to the yeast PEX1 gene, which is necessary for peroxisomal biogenesis [7].
• The peroxin Pex24p of the yeast Yarrowia lipolytica exhibits high sequence similarity to two hypothetical proteins, Yhr150p and Ydr479p, encoded by the Saccharomyces cerevisiae genome [8].
• The yeast gene YKL741 is situated on the left arm of chromosome XI, 12 kb closer to the centromere with respect to the previously localized PAS1 gene [9].

Anatomical context of PEX1

• As has been shown previously for P. pastoris pex1, pex6, and pex22 mutant cells, we show here that pex4Delta mutant cells contain peroxisomal membrane protein-containing peroxisomes that import residual amounts of peroxisomal matrix proteins [10].
• Pex15p of Saccharomyces cerevisiae provides a molecular basis for recruitment of the AAA peroxin Pex6p to peroxisomal membranes [11].
• Within this context, we discuss the proposed role for the endoplasmic reticulum in the formation of preperoxisomes and the potential for 15 Arabidopsis peroxin homologs to function in the biogenesis of peroxisomes in plant cells [12].
• In transiently transformed Arabidopsis and tobacco BY-2 suspension-cultured cells, epitope-tagged AtPex3p (form 2) sorted post-translationally from the cytosol directly to peroxisomes, the first sorting pathway described for any peroxin in plants [13].

Associations of PEX1 with chemical compounds

• Moreover, the levels of 3-hydroxy-3-methylglutaryl CoA reductase and farnesyl diphosphate synthase, two key enzymes in dolichol biosynthesis, are decreased in the absence of a functional PEX1 gene [14].
• However, the severe sucrose dependence of the pex4 pex22 mutant is not accompanied by correspondingly strong defects in peroxisomal matrix protein import, suggesting that this peroxin pair may have novel plant targets in addition to those important in fungi [15].
• Effect of site-directed mutagenesis of conserved lysine residues upon Pas1 protein function in peroxisome biogenesis [16].

Physical interactions of PEX1

• Pex8p, an intraperoxisomal peroxin of Saccharomyces cerevisiae required for protein transport into peroxisomes binds the PTS1 receptor pex5p [17].
• Arabidopsis PEX19 is a dimeric protein that binds the peroxin PEX10 [18].
• Peroxisomal targeting of the Aox complex is abolished in a mutant lacking the peroxin Pex5p, a component of the matrix protein targeting machinery [19].

Other interactions of PEX1

• Northern hybridization experiments further demonstrated that expression of two genes encoding enzymes of peroxisomal beta-oxidation (beta-ketothiolase, trifunctional enzyme) and of a gene involved in peroxisome assembly (PAS1) is also negatively affected by the adr1 null mutation [20].
• PEX11 codes for a peroxin that is critical for normal peroxisome proliferation, and its promoter was shown similarly to contain a UAS1-like element overlapping the ORE [21].
• AFG1, a new member of the SEC18-NSF, PAS1, CDC48-VCP, TBP family of ATPases [22].
• The PAS5 gene was cloned and found to encode a 127-kD protein, which contains a 200-amino acid-long region of homology with PAS1, NEM-sensitive factor (NSF), and other related ATPases [23].
• Ubiquitination of Pex5p is shown to take place exclusively at the peroxisomal membrane after the docking step, and requires the presence of the RING-finger peroxin Pex10p [24].

Analytical, diagnostic and therapeutic context of PEX1

• Analysis of mammalian peroxin interactions using a non-transcription-based bacterial two-hybrid assay [25].
• Using in vitro translation and co-immunoprecipitation AtPEX19-1 was shown to bind to the Arabidopsis peroxisomal membrane protein PEX10 [18].
• We show that Hex1 is localized to the matrix of the Woronin body by immunoelectron microscopy, and that a green fluorescent protein- (GFP-)Hex1 fusion protein is targeted to yeast peroxisomes in a PTS1- and peroxin-dependent manner [26].

References