1. Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm
- Author
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Marianne Antonius, Ann V. Hertzel, Steen Kølvraa, Susanne Mandrup, David A. Bernlohr, Karsten Kristiansen, Torben Helledie, and Rikke V. Sørensen
- Subjects
Transcriptional Activation ,Cytoplasm ,keratinocyte lipid-binding protein/e-FABP/MAL1 ,Peroxisome proliferator-activated receptor ,Gene Expression ,Receptors, Cytoplasmic and Nuclear ,Nerve Tissue Proteins ,QD415-436 ,Fatty Acid-Binding Proteins ,Ligands ,Transfection ,Biochemistry ,Fatty acid-binding protein ,Cell Line ,Mice ,Endocrinology ,Acyl-CoA-binding protein ,Adipocytes ,Animals ,Receptor ,acyl-CoA-binding protein ,Transcription factor ,adipocyte differentiation ,chemistry.chemical_classification ,Cell Nucleus ,Diazepam Binding Inhibitor ,Cell Differentiation ,Cell Biology ,adipocyte lipid-binding protein/a-FABP/aP2 ,3T3 Cells ,Peroxisome ,Neoplasm Proteins ,chemistry ,tetradecylthioacetic acid ,lipids (amino acids, peptides, and proteins) ,Fatty Acid-Binding Protein 7 ,Carrier Proteins ,Nuclear localization sequence ,Transcription Factors - 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 PPARγ 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.—Helledie, T., M. Antonius, R. V. Sørensen, A. V. Hertzel, D. A. Bernlohr, S. Kølvraa, K. Kristiansen, and S. Mandrup. Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm. J. Lipid Res. 2000. 41: 1740–1751.