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Cited by 473

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Identification of Activating Transcription Factor 4 (ATF4) as an Nrf2-interacting Protein

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He, Chuan Hua, Gong, Pengfei, Hu, Bin, Stewart, Daniel, Choi, Mary E., Choi, Augustine M.K., Alam, Jawed·2001·Journal of Biological Chemistry

Abstract

Nrf2 regulates expression of genes encoding enzymes with antioxidant (e.g. heme oxygenase-1 (HO-1)) or xenobiotic detoxification (e.g. NAD(P)H:quinone oxidoreductase, glutathione S-transferase) functions via the stress- or antioxidant-response elements (StRE/ARE). Nrf2 heterodimerizes with small Maf proteins, but the role of such dimers in gene induction is controversial, and other partners may exist. By using the yeast two-hybrid assay, we identified activating transcription factor (ATF) 4 as a potential Nrf2-interacting protein. Association between Nrf2 and ATF4 in mammalian cells was confirmed by co-immunoprecipitation and mammalian two-hybrid assays. Furthermore, Nrf2.ATF4 dimers bound to an StRE sequence from the ho-1 gene. CdCl(2), a potent inducer of HO-1, increased expression of ATF4 in mouse hepatoma cells, and detectable induction of ATF4 protein preceded that of HO-1 (30 min versus 2 h). A dominant-negative mutant of ATF4 inhibited basal and CdCl(2)-stimulated expression of a StRE-dependent/luciferase fusion construct (pE1-luc) in hepatoma cells but only basal expression in mammary epithelial MCF-7 cells. A dominant mutant of Nrf2 was equally inhibitory in both cell types in the presence or absence of CdCl(2). These results indicate that ATF4 regulates basal and CdCl(2)-induced expression of the ho-1 gene in a cell-specific manner and possibly in a complex with Nrf2.

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Metadata

Authors
He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. K., & Alam, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-06
Volume
276
Issue
24
Pages
20858-20865
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2038500334
Cited by
473
References
42
FWCI
6.62
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Identification of Activating Transcription Factor 4 (ATF4) as an Nrf2-interacting Protein. https://app.cochat.ai/papers/10.1074/jbc.m101198200
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He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. K., & Alam, J. (2001). Identification of Activating Transcription Factor 4 (ATF4) as an Nrf2-interacting Protein. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m101198200

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