| First Author | Lo PK | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 40 | Pages | 37186-93 |
| PubMed ID | 11481326 | Mgi Jnum | J:72026 |
| Mgi Id | MGI:2151645 | Doi | 10.1074/jbc.M104701200 |
| Citation | Lo PK, et al. (2001) Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53. J Biol Chem 276(40):37186-93 |
| abstractText | 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, tsp53(Val-135). Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter 1 (THTR-1). Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5 degrees C; upon shifting back to 38.5 degrees C, 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 cells, but not in p53(-/-) mouse embryonic fibroblast 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 THTR-1. |
