High impact information on PEX14

• We have used double-stranded RNA interference to target the PEX14 transcript for degradation [1].
• Here we demonstrate that Pex13 directly binds Pex14 not only via its SH3 domain but also via a novel intraperoxisomal site [2].
• The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7 [2].
• Peroxisome function was affected only mildly by mutations within the novel Pex14 interaction site of Pex13 or by the non-Pex13-interacting mutant Pex5(W204A) [2].
• Based on two-hybrid analyses in mammalian cells and complementary in vitro binding assays, we demonstrate that the evolutionarily conserved pentapeptide repeat motifs, WX(E/D/Q/A/S)(E/D/Q)(F/Y), in PEX5 bind to PEX14 with high affinity [3].

Biological context of PEX14

• Analysis of these complexes revealed that PEX5 possesses multiple binding sites for PEX14, which appear to be distributed throughout its N-terminal half [4].
• Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene [5].
• These findings indicate that there are 13 genotypes in PBD and that the role of PEX14 is also essential in humans [5].
• PEX14 was the only gene that significantly (p=0.03) reduced cell proliferation for both cell types, DFFA significantly (p=0.04) reduced cell proliferation in SK-N-AS but not in HEK293 cells [6].
• The gene encoding NAPP2, PEX14, is located on chromosome 1p36 and is ubiquitously expressed [7].

Anatomical context of PEX14

• Furthermore, we showed that the patient's fibroblasts lacked PEX14 as determined by immunocytochemical analysis [5].
• Although PEX14 mutants have been identified in yeasts and CHO-cells, human PEX14 deficiency has apparently not been documented [5].
• The low sequence identities of PEX14 and PEX5 between parasite and its human host, and the vital importance of proper glycosome biogenesis to the parasite, render these peroxins highly promising drug targets [8].

Associations of PEX14 with chemical compounds

• Surprisingly, procyclic forms, which can grow in the absence of glucose, were killed by PEX14 RNA interference only when simple sugars were present [1].
• We have isolated a protein, NAPP2, which contains an aspartic-acid- and glutamic-acid-rich region and a nuclear localization signal [7].

Other interactions of PEX14

• A pentapeptide motif that is reiterated seven times in PEX5 is proposed as a determinant for the interaction with PEX14 [4].
• Indeed, human PEX14 rescues the import of a PTS1-dependent as well as a PTS2-dependent protein into the peroxisomes in fibroblasts from a patient with Zellweger syndrome belonging to the new complementation group [5].
• The peroxisomal membrane protein PEX14 is a key component of the peroxisomal import machinery and may be the initial docking site for the two import receptors PEX5 and PEX7 [5].
• NAPP2 is thus potentially a negative coregulator of NF-E2 [7].

Analytical, diagnostic and therapeutic context of PEX14

• In mammalian cell culture, ectopically expressed NAPP2 inhibited p45-directed transcriptional activation [7].

References