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  • The EMBO Journal (2007) 26, 835 - 845
  • doi:10.1038/sj.emboj.7601525

Published online: 25 January 2007

Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in bold beta-oxidation of fatty acids

Igor V Kurochkin1,1, Yumi Mizuno2, Akihiko Konagaya3, Yoshiyuki Sakaki4, Christian Schönbach1,b and Yasushi Okazaki2

  1. Immunoinformatics Team, Advanced Genome Information Group, RIKEN Genomic Sciences Center, Yokohama, Japan
  2. Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Hidaka-shi, Saitama, Japan
  3. RIKEN Genomic Sciences Center, Yokohama, Japan
  4. Computational and Experimental Systems Biology Group, RIKEN Genomic Sciences Center, Yokohama, Japan

Correspondence to:

Igor V Kurochkin, IV Kurochkin, Genome Annotation and Comparative Analysis Team, Computational and Experimental Systems Biology Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Tel.: +81 45 503 9111 (ext 8106); Fax: +81 45 503 9176; E-mail: igork@gsc.riken.jp

Yasushi Okazaki, Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-city, Saitama 350-1241, Japan. Tel.: +81 42 985 7319; Fax: +81 42 985 7329; E-mail: okazaki@saitama-med.ac.jp

aPresent address: Genome Annotation and Comparative Analysis Team, Computational and Experimental Systems Biology Group, RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan

bPresent address: Division of Genomics and Genetics, School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore

Received 23 June 2006; Accepted 5 December 2006

Peroxisomes play an important role in beta-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 beta-oxidation. Tysnd1 itself undergoes processing through the removal of the presumably inhibitory N-terminal fragment. Tysnd1 expression is induced by the proliferator-activated receptor alpha 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 beta-oxidation.

  • Keywords:

    • fatty acid oxidation,
    • peroxisomes,
    • protease,
    • protein processing,
    • Tysnd1