title: Identification and characterization of interactions between abscisic acid and human heat shock protein 70 family members.
abstract: Abscisic acid (ABA) is a stress-inducible plant hormone comprising an inevitable component of the human diet. Recently, stress-induced accumulation of autocrine ABA was shown in humans, as well as ABA-mediated modulation of a number of disease-associated systems. Now, the application of a chemical proteomics approach to gain further insight into ABA mechanisms of action in mammalian cells is reported. An ABA mimetic photoaffinity probe was applied to intact mammalian insulinoma and embryonic cells, leading to the identification of heat shock protein 70 (HSP70) family members, (including GRP78 and HSP70-2) as putative human ABA-binding proteins. In vitro characterization of the ABA-HSP70 interactions yielded K(d)s in the 20-60 µM range, which decreased several fold in the presence of co-chaperone. However, ABA was found to have only variable- and co-chaperone-independent effects on the ATPase activity of these proteins. The potential implications of these ABA-HSP70 interactions are discussed with respect to the intracellular protein folding and extracellular receptor-like activities of these stress-inducible proteins. While mechanistic and functional relevance remain enigmatic, we conclude that ABA can bind to human HSP70 family members with physiologically relevant affinities and in a co-chaperone-dependent manner.
authors: Plant Biotechnology Institute, National Research Council of Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan, S7N 0W9; Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada and Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada.
authors: Olesya A
authors: OA
authors: Kharenko
authors: Devin
authors: D
authors: Polichuk
authors: Ken M
authors: KM
authors: Nelson
authors: Suzanne R
authors: SR
authors: Abrams
authors: Michele C
authors: MC
authors: Loewen
mesh_terms: D000040:Abscisic Acid / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D057809:HEK293 Cells; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D040901:Proteomics; D051381:Rats
chemical_list: C107481:DNAJA1 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D000040:Abscisic Acid
keywords: Heat shock protein 70; abscisic acid; chemical proteomics; glucose-regulated protein 78; protein–ligand interaction