p53 is a mediator for radiation-repressed human TR2 orphan receptor expression in MCF-7 cells, a new pathway from tumor suppressor to member of the steroid receptor superfamily.
p53 may function as a checkpoint by arresting the G1 cell cycle in response to DNA damage induced by radiation or other stimuli. We have found that the expression of the TR2 orphan receptor (TR2), a member of the steroid receptor superfamily, was down-regulated by ionizing irradiation. Our data shown in the present study demonstrate that irradiation can repress TR2 at both the translational and transcriptional levels. Transient transfection assays further link p53 to this repression by proving that endogenously induced or exogenously transfected p53 can repress TR2 gene expression, and this repression can be reversed by the co-transfection of SV40 large T antigen. Together, our data demonstrate for the first time that radiation and p53 can repress TR2, possibly providing a new pathway to link ionizing irradiation and p53 to members of the steroid receptor superfamily.
Lin
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DL
Department of Medicine and University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison, 53792, USA.
Chang
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C
D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis; D001943:Breast Neoplasms; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000528:radiation effects*; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D014176:Protein Biosynthesis / Q000187:drug effects; D011987:Receptors, Steroid / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D013539:Simian virus 40 / Q000276:immunology; D014158:Transcription, Genetic / Q000528:radiation effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; C539822:NR2C1 protein, human; D009687:Nuclear Proteins; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase