Mammalian cells respond to low oxygen by inducing the transcription of a diverse set of genes, which participate in many physiological and pathological processes. We identified hypoxia as an inducer of human (h)MT-IIA expression and now show that mouse (m)MT-1 is similarly responsive. Using reporter analyses we localized hypoxia-response elements of the hMT-IIA and mMT-1 promoters to the metal response elements MREa and MREd, respectively. Studies with a MRE-binding transcription factor-1 (MTF-1) knockout fibroblasts indicated its involvement in hypoxic-induction of both genes. Other studies using transdominant interfering mutants and inhibitors imply the involvement of a stress inducible pathway(s) consisting of Ras, PI3-kinase. and PKC. These studies provide evidence for the transcriptional control of a gene by hypoxia that is not HIF-1 dependent, and for mutifunctional roles of MREs.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology