Activation-induced down-regulation of retinoid receptor RXRalpha expression in human T lymphocytes. Role of cell cycle regulation.
A 5.4-kilobase mRNA, the expression of which is down-regulated 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 RXRalpha mRNA. Here, we report the nucleotide sequence of 3.6 kilobases of this RNA, which represents the 3' end of RXRalpha mRNA, the sequence of which has not been previously described. Activated PBMCs also expressed lower levels of RXRalpha protein, and a DNA binding assay showed that the activation-induced loss of RXRalpha mRNA and protein expression correlated with the loss of DNA binding activity of this protein. We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of RXRalpha expression and that cell cycle inhibitors, which block the cells in G1 phase, prevent this down-regulation. The decrease in the levels of RXRalpha mRNA was found to be regulated at the post-transcriptional level and involved new protein synthesis. These observations indicate that the levels of RXRalpha expression in T lymphocytes are coupled to cell cycle progression, and there is tight regulatory control of RXRalpha expression during the transition from G0/G1 to S phase of the cell cycle.
Laboratory of Molecular Cell Biology, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
M
M
Ishaq
Y M
YM
Zhang
V
V
Natarajan
D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D002453:Cell Cycle; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D017931:DNA Primers; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D013601:T-Lymphocytes / Q000378:metabolism*
D017252:CD3 Complex; D017931:DNA Primers; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D003609:Dactinomycin; D016572:Cyclosporine; D003513:Cycloheximide