Hypoxia-Inducible Factor-1α Obstructs a Wnt Signaling Pathway by Inhibiting the hARD1-Mediated Activation of β-Catenin
| العنوان: | Hypoxia-Inducible Factor-1α Obstructs a Wnt Signaling Pathway by Inhibiting the hARD1-Mediated Activation of β-Catenin |
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| المؤلفون: | Yang Sook Chun, Ji Hong Lim, Jong Wan Park |
| المصدر: | Cancer Research. 68:5177-5184 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cancer Research, Plasma protein binding, Biology, Models, Biological, Proto-Oncogene Proteins c-myc, Proto-Oncogene Proteins p21(ras), Acetyltransferases, Humans, N-Terminal Acetyltransferase E, Cells, Cultured, N-Terminal Acetyltransferase A, beta Catenin, Cell Proliferation, Cell growth, HEK 293 cells, Wnt signaling pathway, Acetylation, HCT116 Cells, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, Cell biology, Wnt Proteins, Gene Expression Regulation, Oncology, Hypoxia-inducible factors, Biochemistry, Catenin, Signal transduction, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, Protein Binding, Signal Transduction |
| الوصف: | Although a splice variant of mouse mARD1s was found to acetylate and destabilize hypoxia-inducible factor-1α (HIF-1α), human hARD1 has no such activities. Nonetheless, hARD1 has been reported to bind directly with HIF-1α. Here, we addressed the functional significance of the hARD1–HIF-1α interaction. Because hARD1 acetylates and activates β-catenin, we examined whether HIF-1α regulates the hARD1-mediated activation of Wnt signaling. It was found that HIF-1α binds hARD1 through the oxygen-dependent degradation domain and, in so doing, dissociates hARD1 from β-catenin, which prevents β-catenin acetylation. In LiCl-stimulated HEK293 or cancer cell lines with active Wnt signaling, β-catenin acetylation and activity were suppressed in hypoxia, and these suppressions were mediated by HIF-1α. Moreover, HIF-1α disruption of hARD1/β-catenin repressed TCF4 activity, resulting in c-Myc suppression and p21cip1 induction. In addition, we confirmed that the HIF-1α NH2 terminal inactivates TCF4 by directly binding β-catenin. In conclusion, HIF-1α was found to inactivate the Wnt signaling by binding to hARD1 or β-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells. [Cancer Res 2008;68(13):5177–84] |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::844c03bde70b24b6b944c271abc126bfTest https://doi.org/10.1158/0008-5472.can-07-6234Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....844c03bde70b24b6b944c271abc126bf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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