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Negative regulation of hypoxia inducible factor‐1α by necdin
Author(s) -
Moon Hyo-Eun,
Ahn Mee-Young,
Park Jeong Ae,
Min Kyung-Jin,
Kwon Yoo-Wook,
Kim Kyu-Won
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.072
Subject(s) - erythropoiesis , downregulation and upregulation , transcription factor , hypoxia inducible factors , regulator , angiogenesis , chemistry , hypoxia (environmental) , immunoprecipitation , microbiology and biotechnology , hypoxia inducible factor 1 , suppressor , biochemistry , cancer research , oxygen , biology , medicine , gene , organic chemistry , anemia
Hypoxia‐inducible factor 1 (HIF‐1) is a master transcription factor that mediates cellular and systemic homeostatic responses to reduce O 2 availability, such as erythropoiesis, angiogenesis, and glycolysis. Using the yeast two‐hybrid screening system, we found that the oxygen dependent degradation (ODD) domain of HIF‐1α interacts with necdin, a growth suppressor. The interaction of necdin with HIF‐1α was confirmed using coimmunoprecipitation with the overexpressed HIF‐1α. Biological effect of necdin on HIF‐1α showed that necdin reduces the transcriptional activity of HIF‐1 under hypoxia. Moreover, necdin decreased the level of the HIF‐1α protein, but not that of mRNA, implying a possibility of necdin‐mediated HIF‐1α degradation. Furthermore, necdin has an anti‐angiogenic activity in the tube formation assay and CAM assay, which might be due to the downregulation of HIF‐1α. Collectively, these results suggest that necdin can be a novel negative regulator of HIF‐1α stability via the direct interaction.