Cross talk of insulin resistance and vitamin A metabolism

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Retinol binding protein 4 (RBP4) is the transport protein that carries retinol in blood. Mice lacking glucose transporter 4 (GLUT4) in adipocytes have enhanced Rbp4 gene expression; however, the molecular mechanism is unknown. We found a G4KA (GLUT4 knockdown-dependent transcriptional activation) element located 1.3 kb upstream of the Rbp4 promoter. In a yeast one-hybrid screen of a G4KD-L1 (GLUT4 knockdown 3T3-L1) adipocyte cell cDNA library, using the G4KA element as bait, we identified subunit of the 20 S proteasome, PSMB1. PSMB1 was tightly bound to G4KA. PSMB1 RNA interference inhibited Rbp4 transcription. Nuclear transportation of PSMB1 was increased in G4KD-L1 cells. The putative tyrosine phosphorylation site in PSMB1 was mutated to phenylalanine (Y149F). Y149F PSMB1 displayed increased nuclear translocation, resulting in activation of transcription in adipocytes. We propose that modulation of PSMB1 nuclear localization can be influenced by the phosphorylation status of PSMB1.