Transcriptional repression of taurine transporter gene (TauT) by p53 in renal cells.
Taurine, an intracellular osmolyte whose body pool size is adaptively regulated by the kidney, is required for normal renal development. Overexpression of the p53 tumor suppressor gene in p53 transgenic mice results in renal malformation, suggesting that altered expression of certain p53 target gene(s) involved in renal development may be responsible. This study shows that the taurine transporter gene (TauT) is a transcriptional target of p53. Expression of TauT was decreased after activation of p53 by doxorubicin, a DNA-damaging drug, in 293 and NRK-52E renal cells. TauT promoter activity was decreased 5-10-fold by cotransfection of a full-length TauT promoter-reporter construct with p53, which was reversed by cotransfection with a mutant p53 (p53-281). Electrophoretic mobility shift assays using nuclear extracts from p53-expressing (10)1val cells showed a putative p53-binding site in the TauT promoter region, which bound to the p53 in electrophoretic mobility shift assays. Mutation of this p53 consensus sequence abolished binding of p53. These results demonstrate that TauT may represent a downstream target gene of p53 that could link the roles of p53 in renal development and apoptosis.
Han
Xiaobin
X
Department of Pediatrics, University of Tennessee Health Science Center and the Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee 38103, USA.
Patters
Andrea Budreau
AB
Chesney
Russell W
RW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D017930:Genes, Reporter; D016158:Genes, p53; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000196:embryology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013552:Swine; D013654:Taurine / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000099247:Taurine Transporters
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004317:Doxorubicin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D016159:Tumor Suppressor Protein p53; D000099247:Taurine Transporters