Activation-Induced Down-Regulation of Retinoid Receptor Rxr-Alpha Expression in Human T Lymphocytes - Role of Cell Cycle Regulation

A 5.4-kilobase mRNA, the expression of which is downregulated after treatment of human peripheral blood mononuclear cells (PBMCs) with various T cell-activating agents, was isolated using an mRNA differential display method. Nucleotide sequence analysis identified the 5' end of this RNA as human retinoid receptor RXR alpha mRNA. Here, we report the nucleotide sequence of 3.6 kilobases of this RNA, which represents the 3' end of RXR alpha mRNA, the sequence of which has not been previously described. Activated PBMCs also expressed lower levels of RXR alpha protein, and a DNA binding assay showed that the activation-induced loss of RXRa mRNA and protein expression correlated with the loss of DNA binding activity of this protein. We present evidence that the transition from G(0)/G(1) to S phase of the cell cycle results in the down-regulation of RXR alpha expression and that cell cycle inhibitors, which block the cells in G(1) phase, prevent this down-regulation. The decrease in the levels of RXR alpha mRNA was found to be regulated at the posttranscriptional level and involved new protein synthesis. These observations indicate that the levels of RXR alpha expression in T lymphocytes are coupled to cell cycle progression, and there is tight regulatory control of RXR alpha expression during the transition from G(0)/G(1) to S phase of the cell cycle. [References: 41]

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