Cross talk of insulin resistance and vitamin A metabolism

视黄醇结合蛋白4（RBP 4）是在血液中携带视黄醇的转运蛋白。脂肪细胞中缺乏葡萄糖转运蛋白4（GLUT 4）的小鼠Rbp 4基因表达增强;然而，分子机制尚不清楚。我们发现一个G4 KA（GLUT 4敲低依赖的转录激活）元件位于Rbp 4启动子上游1.3 kb。在酵母单杂交筛选G4 KD-L1（GLUT 4敲低3 T3-L1）脂肪细胞cDNA文库中，以G4 KA元件为诱饵，我们鉴定了20 S蛋白酶体的亚基PSMB 1。PSMB 1与G4 KA紧密结合。PSMB 1 RNA干扰抑制Rbp 4的转录。在G4 KD-L1细胞中，PSMB 1的核转运增加。PSMB 1中假定的酪氨酸磷酸化位点突变为苯丙氨酸（Y149 F）。Y149 F PSMB 1显示增加的核转位，导致脂肪细胞中的转录激活。我们认为PSMB 1的磷酸化状态可以影响PSMB 1核定位的调节。

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.