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Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lim, Ji-Hong | - |
dc.contributor.author | Chun, Yang-Sook | - |
dc.contributor.author | Park, Jong-Wan | - |
dc.date.accessioned | 2010-06-25T06:41:48Z | - |
dc.date.available | 2010-06-25T06:41:48Z | - |
dc.date.issued | 2008-07-03 | - |
dc.identifier.citation | Cancer Res. 2008;68(13):5177-84 | en |
dc.identifier.issn | 1538-7445 (Electronic) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18593917 | - |
dc.identifier.uri | http://cancerres.aacrjournals.org/cgi/reprint/68/13/5177.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67800 | - |
dc.description.abstract | Although a splice variant of mouse mARD1s was found to acetylate and destabilize hypoxia-inducible factor-1alpha (HIF-1alpha), human hARD1 has no such activities. Nonetheless, hARD1 has been reported to bind directly with HIF-1alpha. Here, we addressed the functional significance of the hARD1-HIF-1alpha interaction. Because hARD1 acetylates and activates beta-catenin, we examined whether HIF-1alpha regulates the hARD1-mediated activation of Wnt signaling. It was found that HIF-1alpha binds hARD1 through the oxygen-dependent degradation domain and, in so doing, dissociates hARD1 from beta-catenin, which prevents beta-catenin acetylation. In LiCl-stimulated HEK293 or cancer cell lines with active Wnt signaling, beta-catenin acetylation and activity were suppressed in hypoxia, and these suppressions were mediated by HIF-1alpha. Moreover, HIF-1alpha disruption of hARD1/beta-catenin repressed TCF4 activity, resulting in c-Myc suppression and p21(cip1) induction. In addition, we confirmed that the HIF-1alpha NH(2) terminal inactivates TCF4 by directly binding beta-catenin. In conclusion, HIF-1alpha was found to inactivate the Wnt signaling by binding to hARD1 or beta-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells. | en |
dc.language.iso | en | en |
dc.publisher | American Association for Cancer Research | en |
dc.subject | Acetylation | en |
dc.subject | Acetyltransferases/metabolism/*physiology | en |
dc.subject | Cell Hypoxia/physiology | en |
dc.subject | Cell Proliferation | en |
dc.subject | Cells, Cultured | en |
dc.subject | Gene Expression Regulation | en |
dc.subject | HCT116 Cells | en |
dc.subject | Humans | en |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/*physiology | en |
dc.subject | Models, Biological | en |
dc.subject | Protein Binding | en |
dc.subject | Proto-Oncogene Proteins c-myc/genetics | en |
dc.subject | Proto-Oncogene Proteins p21(ras)/genetics/metabolism | en |
dc.subject | Signal Transduction | en |
dc.subject | TCF Transcription Factors/antagonists & inhibitors/metabolism | en |
dc.subject | Wnt Proteins/*antagonists & inhibitors | en |
dc.subject | beta Catenin/*metabolism | en |
dc.title | Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 임지홍 | - |
dc.contributor.AlternativeAuthor | 전양숙 | - |
dc.contributor.AlternativeAuthor | 박종완 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-07-6234 | - |
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