Glutathione transferase P1 is modified by palmitate

被引:0
作者
Marensi, Vanessa [1 ,2 ,5 ,6 ]
Yap, Megan C. [3 ]
Ji, Yuhuan [4 ,7 ]
Lin, Cheng [4 ]
Berthiaume, Luc G. [3 ]
Leslie, Elaine M. [1 ,2 ]
机构
[1] Univ Alberta, Fac Med & Dent, Dept Physiol, Edmonton, AB, Canada
[2] Univ Alberta, Fac Med & Dent, Membrane Prot Dis Res Grp, Edmonton, AB, Canada
[3] Univ Alberta, Fac Med & Dent, Dept Cell Biol, Edmonton, AB, Canada
[4] Boston Univ, Chobanian & Avedisian Sch Med, Dept Biochem & Cell Biol, Ctr Biomed Mass Spectrometry, Boston, MA USA
[5] Univ Chester, Chester Med Sch, Chester, England
[6] Univ Liverpool, Inst Syst Mol & Integrat Biol, Dept Biochem & Syst Biol, Liverpool, England
[7] Resolian Bioanalyt Chongqing, Chongqing, Peoples R China
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院; 美国国家卫生研究院;
关键词
FATTY-ACID ACYLATION; S-TRANSFERASE; OXIDATIVE STRESS; ETHACRYNIC-ACID; PROTEIN; PALMITOYLATION; PI; MEMBRANE; IDENTIFICATION; COMPLEX;
D O I
10.1371/journal.pone.0308500
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Glutathione transferase P1 (GSTP1) is a multi-functional protein that protects cells from electrophiles by catalyzing their conjugation with glutathione, and contributes to the regulation of cell proliferation, apoptosis, and signalling. GSTP1, usually described as a cytosolic enzyme, can localize to other cell compartments and we have reported its strong association with the plasma membrane. In the current study, the hypothesis that GSTP1 is palmitoylated and this modification facilitates its dynamic localization and function was investigated. Palmitoylation is the reversible post-translational addition of a 16-C saturated fatty acid to proteins, most commonly on Cys residues through a thioester bond. GSTP1 in MCF7 cells was modified by palmitate, however, GSTP1 Cys to Ser mutants (individual and Cys-less) retained palmitoylation. Treatment of palmitoylated GSTP1 with 0.1 N NaOH, which cleaves ester bonds, did not remove palmitate. Purified GSTP1 was spontaneously palmitoylated in vitro and peptide sequencing revealed that Cys48 and Cys102 undergo S-palmitoylation, while Lys103 undergoes the rare N-palmitoylation. N-palmitoylation occurs via a stable NaOH-resistant amide bond. Analysis of subcellular fractions of MCF7-GSTP1 cells and a modified proximity ligation assay revealed that palmitoylated GSTP1 was present not only in the membrane fraction but also in the cytosol. GSTP1 isolated from E. coli, and MCF7 cells (grown under fatty acid free or regular conditions), associated with plasma membrane-enriched fractions and this association was not altered by palmitoyl CoA. Overall, GSTP1 is modified by palmitate, at multiple sites, including at least one non-Cys residue. These modifications could contribute to regulating the diverse functions of GSTP1.
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页数:28
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