title: Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm.
abstract: Peroxisome proliferator-activated receptors (PPARs) are activated by a variety of fatty acids, eicosanoids, and hypolipidemic and insulin-sensitizing drugs. Many of these compounds bind avidly to members of a family of small lipid-binding proteins, the fatty acid-binding proteins (FABPs). Fatty acids are activated to CoA esters, which bind with high affinity to the acyl-CoA-binding protein (ACBP). Thus, the availability of known and potential PPAR ligands may be regulated by lipid-binding proteins. In this report we show by transient transfection of CV-1 cells that coexpression of ACBP and adipocyte lipid-binding protein (ALBP) exerts a ligand- and PPAR subtype-specific attenuation of PPAR-mediated trans-activation, suggesting that lipid-binding proteins, when expressed at high levels, may function as negative regulators of PPAR activation by certain ligands. Expression of ACBP, ALBP, and keratinocyte lipid-binding protein (KLBP) is induced during adipocyte differentiation, a process during which PPARgamma plays a prominent role. We present evidence that endogenous ACBP, ALBP, and KLBP not only localize to the cytoplasm but also exhibit a prominent nuclear localization in 3T3-L1 adipocytes. In addition, forced expression of ACBP, ALBP, and KLBP in CV-1 cells resulted in a substantial accumulation of all three proteins in the nucleus. These results suggest that lipid-binding proteins, contrary to the general assumption, may exert their action in the nucleus as well as in the cytoplasm.
authors.affiliation: Department of Molecular Biology, University of Southern Denmark, Odense, DK-5230 Odense M, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Helledie
authors.forename: M
authors.initials: M
authors.lastname: Antonius
authors.forename: R V
authors.initials: RV
authors.lastname: Sorensen
authors.forename: A V
authors.initials: AV
authors.lastname: Hertzel
authors.forename: D A
authors.initials: DA
authors.lastname: Bernlohr
authors.forename: S
authors.initials: S
authors.lastname: Kølvraa
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
authors.forename: S
authors.initials: S
authors.lastname: Mandrup
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D026261:Diazepam Binding Inhibitor; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D015870:Gene Expression; D008024:Ligands; D051379:Mice; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors