Transcriptional regulation of human metallothionein-IIA and mouse MT-I by hypoxia involves a metal response element

B. J. Murphy, G. K. Andrews, A. M. Giaccia, C. J. Green, D. Discher, D. Bittel, K. R. Laderoute, K. A. Webster

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
Pages (from-to)A1380
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Murphy, B. J., Andrews, G. K., Giaccia, A. M., Green, C. J., Discher, D., Bittel, D., Laderoute, K. R., & Webster, K. A. (1997). Transcriptional regulation of human metallothionein-IIA and mouse MT-I by hypoxia involves a metal response element. FASEB Journal, 11(9), A1380.