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M104701200v1
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Papers In Press, published online ahead of print July 31, 2001
J. Biol. Chem, 10.1074/jbc.M104701200
Submitted on May 23, 2001
Revised on July 19, 2001
Accepted on July 31, 2001

Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53

Pang-Kuo Lo, Jeuo-Yuan Chen, Pi-Pei Tang, Jiayuh Lin, Chi-Hung Lin, Li-Ting Su, Chia-Hui Wu, Tse-Ling Chen, Yin Yang, and Fung-Fang Wang

Biochemistry, National Yang-Ming University, Taipei 112

Corresponding Author: ffwang{at}ym.edu.tw

p53 tumor suppressor is a transcription factor that functions, in part, through many of its downstream target genes. We have identified a p53 inducible gene by performing mRNA differential display on IW32 murine erythroleukemia cells containing a temperature-sensitive p53 mutant allele, tsp53val-135. Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter THTR-1. Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5oC; upon shifting back to 38.5oC, mTHTR-1 transcript was rapidly degraded with a half-life of less than 2 h. Elevation of mTHTR-1 expression was found in DNA damage induced normal mouse embryonic fibroblast (MEF) cells, but not in p53-/- MEF cells, suggesting that mTHTR-1 induction was p53 dependent. A region within the first intron of the mTHTR-1 gene bound to p53 and conferred the p53-mediated transactivation. Furthermore, increased thiamine transporter activities were found in cells overexpressing mTHTR-1, and under conditions of DNA damage or p53 activation. Our findings indicate that p53 may be involved in maintaining thiamine homeostasis through transactivation of the thiamine transporter THTR-1.


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