| Summary: | 碩士 === 國立陽明大學 === 生物化學研究所 === 90 === Abstract
The p53 tumor suppressor functions as a guardian of genome and plays a central role in cellular response to aberrant growth signals and certain cytotoxic stresses. Identification of p53 target genes is important to elucidate the molecular mechanisms underlying p53-induced biological pathways.
By the method of mRNA differential display, we have previously identified the mouse thiamine transporter (mTHTR-1) as a p53 direct transcriptional target gene. Immunohistochemistry studies of mouse brain revealed mTHTR-1 was specifically expressed in the hypothalamus. Further analysis mapped mTHTR-1 expression to the preoptic and paraventricular nucleus. Similar mTHTR-1 expression patterns were found in the p53 knockout mice, suggesting that basal expression of mTHTR-1 in the hypothalamus is governed by a p53-independet mechanism. Luciferase reporter analysis indicated that p53 response element of mTHTR-1 conferred that transactivation mediated by members of the p73 family proteins. Induction of mTHTR-1 mRNA was found in -irradiation or cisplatin treated normal mouse embryonic fibroblast (MEF) cells, but not in p53 knockout MEFs. These findings demonstrated that mTHTR-1 is a potential transcriptional target gene of p73.
Taken together, these result showed that mTHTR-1 was specifically expressed in the hypothalamus of the brain, and it’s basal expression could be regulated by a p53-independent pathway. The functional significance of mTHTR-1 expression in the hypothalamus remains to be elucidated.
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