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| Content Provider | PubMed Central |
|---|---|
| Author | Zhang, Peng Bai, Yan Ling, Lu Yun, Li Duan, Cunming |
| Editor | Whitfield, Tanya T. |
| Copyright Year | 2016 |
| Abstract | Hypoxia-inducible factors (HIFs), while best known for their roles in the hypoxic response, have oxygen-independent roles in early development with poorly defined mechanisms. Here, we report a novel Hif-3α variant, Hif-3α2, in zebrafish. Hif-3α2 lacks the bHLH, PAS, PAC, and ODD domains, and is expressed in embryonic and adult tissues independently of oxygen availability. Hif-3α2 is a nuclear protein with significant hypoxia response element (HRE)-dependent transcriptional activity. Hif-3α2 overexpression not only decreases embryonic growth and developmental timing but also causes left-right asymmetry defects. Genetic deletion of Hif-3α2 by CRISPR/Cas9 genome editing increases, while Hif-3α2 overexpression decreases, Wnt/β-catenin signaling. This action is independent of its HRE-dependent transcriptional activity. Mechanistically, Hif-3α2 binds to β-catenin and destabilizes the nuclear β-catenin complex. This mechanism is distinct from GSK3β-mediated β-catenin degradation and is conserved in humans. These findings provide new insights into the oxygen-independent actions of HIFs and uncover a novel mechanism regulating Wnt/β-catenin signaling. |
| Related Links | http://dx.doi.org/10.7554/eLife.08996 |
| Starting Page | 8996 |
| File Format | |
| ISSN | 2050084X |
| e-ISSN | 2050084X |
| Journal | eLife |
| Volume Number | 5 |
| Language | English |
| Publisher | eLife Sciences Publications, Ltd |
| Publisher Date | 2016-01-14 |
| Access Restriction | Open |
| Rights Holder | eLife Sciences Publications, Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology |
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