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Background: Coronary artery lesions (CAL) are a serious complication of Kawasaki disease (KD). The increased serum E-selectin level during the acute phase of KD and the association of E-selectin gene ( SELE) polymorphisms with the prevalence of coronary artery disease in adults suggest a possible association between SELE polymorphisms and the development of CAL in KD patients. Methods: The subjects consisted of 177 KD patients, including 59 with and 118 without CAL, and 305 healthy controls. Two single nucleotide polymorphisms (SNP) of SELE, 98G>T (rs1805193) and Ser128Arg (rs5361), were genotyped by direct sequencing and the high-resolution melting curve method, respectively. The allele distributions were assessed using the chi-squared test. Results: There were no significant differences in the T allele frequency at 98G>T between KD patients and controls (1.4% vs 1.0%, P= 0.55) or between KD patients with and without CAL (1.7% vs 1.3%, P= 0.77). Similarly, there were no differences in the distribution of the C allele (128Arg) at Ser128Arg between KD patients and controls (4.5% vs 3.4%, P= 0.40) or between KD patients with and without CAL (4.2% vs 4.7%, P= 0.86). Conclusion: Although no association was detected between these SELE polymorphisms and the prevalence of KD or the development of CAL, this may have been due to the study limitations, including a low frequency of the minor alleles and a small sample size. A larger-scale association study is needed in order for a definitive conclusion to be made as to whether these SNP are associated with susceptibility to KD or not. [ABSTRACT FROM AUTHOR]

Background: The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences. Results: We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARa mediated activation. Notably, none of the PTS2 candidates located to peroxisomes. Conclusion: In a few cases the PTS may oscillate from "silent" to "functional" depending on its surface accessibility indicating the potential for context-dependent conditional subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve without generation and integration of new experimental data from location proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays. [ABSTRACT FROM AUTHOR]

Peroxisomes play an important role in β-oxidation of fatty acids. All peroxisomal matrix proteins are synthesized in the cytosol and post-translationally sorted to the organelle. Two distinct peroxisomal signal targeting sequences (PTSs), the C-terminal PTS1 and the N-terminal PTS2, have been defined. Import of precursor PTS2 proteins into the peroxisomes is accompanied by a proteolytic removal of the N-terminal targeting sequence. Although the PTS1 signal is preserved upon translocation, many PTS1 proteins undergo a highly selective and limited cleavage. Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. Tysnd1 itself undergoes processing through the removal of the presumably inhibitory N-terminal fragment. Tysnd1 expression is induced by the proliferator-activated receptor α agonist bezafibrate, along with the increase in its substrates. A model is proposed where the Tysnd1-mediated processing of the peroxisomal enzymes promotes their assembly into a supramolecular complex to enhance the rate of β-oxidation. [ABSTRACT FROM AUTHOR]