RRC ID 37106
著者 Uyama T, Kawai K, Kono N, Watanabe M, Tsuboi K, Inoue T, Araki N, Arai H, Ueda N.
タイトル Interaction of Phospholipase A/Acyltransferase-3 with Pex19p: A POSSIBLE INVOLVEMENT IN THE DOWN-REGULATION OF PEROXISOMES.
ジャーナル J Biol Chem
Abstract Phospholipase A/acyltransferase (PLA/AT)-3 (also known as H-rev107 or AdPLA) was originally isolated as a tumor suppressor and was later shown to have phospholipase A1/A2 activity. We have also found that the overexpression of PLA/AT-3 in mammalian cells results in specific disappearance of peroxisomes. However, its molecular mechanism remained unclear. In the present study, we first established a HEK293 cell line, which stably expresses a fluorescent peroxisome marker protein (DsRed2-Peroxi) and expresses PLA/AT-3 in a tetracycline-dependent manner. The treatment with tetracycline, as expected, caused disappearance of peroxisomes within 24 h, as revealed by diffuse signals of DsRed2-Peroxi and a remarkable decrease in a peroxisomal membrane protein, PMP70. A time-dependent decrease in ether-type lipid levels was also seen. Because the activation of LC3, a marker of autophagy, was not observed, the involvement of autophagy was unlikely. Among various peroxins responsible for peroxisome biogenesis, Pex19p functions as a chaperone protein for the transportation of peroxisomal membrane proteins. Immunoprecipitation analysis showed that PLA/AT-3 binds to Pex19p through its N-terminal proline-rich and C-terminal hydrophobic domains. The protein level and enzyme activity of PLA/AT-3 were increased by its coexpression with Pex19p. Moreover, PLA/AT-3 inhibited the binding of Pex19 to peroxisomal membrane proteins, such as Pex3p and Pex11βp. A catalytically inactive point mutant of PLA/AT-3 could bind to Pex19p but did not inhibit the chaperone activity of Pex19p. Altogether, these results suggest a novel regulatory mechanism for peroxisome biogenesis through the interaction between Pex19p and PLA/AT-3.
巻・号 290(28)
ページ 17520-34
公開日 2015-7-10
DOI 10.1074/jbc.M114.635433
PII S0021-9258(20)35353-9
PMID 26018079
PMC PMC4498086
MeSH Animals COS Cells Chlorocebus aethiops Down-Regulation HEK293 Cells Humans Lipoproteins / chemistry Lipoproteins / genetics Lipoproteins / metabolism Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Models, Biological Peroxins Peroxisomes / metabolism* Phospholipases A2, Calcium-Independent / chemistry Phospholipases A2, Calcium-Independent / genetics Phospholipases A2, Calcium-Independent / metabolism* Protein Interaction Domains and Motifs Recombinant Proteins / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Tumor Suppressor Proteins / chemistry Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 4.238
引用数 12
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Hepa 1-6(RCB1638)