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- W4362492022 abstract "<div>Abstract<p>Mammalian <i>metallothionein</i> (<i>MT</i>) genes are transcriptionally activated by the essential metal zinc as well as by environmental stresses, including toxic metal overload and redox fluctuations. In addition to playing a key role in zinc homeostasis, MT proteins can protect against metal- and oxidant-induced cellular damage, and may participate in other fundamental physiologic and pathologic processes such as cell survival, proliferation, and neoplasia. Previously, our group reported a requirement for metal-responsive transcription factor-1 (MTF-1) in hypoxia-induced transcription of mouse <i>MT-I</i> and human <i>MT-IIA</i> genes. Here, we provide evidence that the protumorigenic hypoxia-inducible transcription factor-1α (HIF-1α) is essential for induction of <i>MT-1</i> by hypoxia, but not zinc. Chromatin immunoprecipitation assays revealed that MTF-1 and HIF-1α are both recruited to the mouse <i>MT-I</i> promoter in response to hypoxia, but not zinc. In the absence of HIF-1α, MTF-1 is recruited to the <i>MT-I</i> promoter but fails to activate <i>MT-I</i> gene expression in response to hypoxia. Thus, HIF-1α seems to function as a coactivator of <i>MT-I</i> gene transcription by interacting with MTF-1 during hypoxia. Coimmunoprecipitation studies suggest interaction between MTF-1 and HIF-1α, either directly or as mediated by other factors. It is proposed that association of these important transcription factors in a multiprotein complex represents a common strategy to control unique sets of hypoxia-inducible genes in both normal and diseased tissue. (Mol Cancer Res 2008;6(3):483–90)</p></div>" @default.
- W4362492022 created "2023-04-05" @default.
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- W4362492022 date "2023-04-03" @default.
- W4362492022 modified "2023-09-29" @default.
- W4362492022 title "Data from Metallothionein Induction by Hypoxia Involves Cooperative Interactions between Metal-Responsive Transcription Factor-1 and Hypoxia-Inducible Transcription Factor-1α" @default.
- W4362492022 doi "https://doi.org/10.1158/1541-7786.c.6541456.v1" @default.
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