Abstract
von Hippel-Lindau-binding protein 1 (VBP1) physically interacts with pVHL, an E3-ubiquitin ligase, which degrades HIF-1α in an oxygen-dependent manner. HIF-1 is a key regulator of adaptive responses to a lack of oxygen that controls glucose metabolism, angiogenesis, proliferation, invasion, and metastasis. However, the role of VBP1 in pVHL-mediated degradation of HIF-1α is not yet known. In this study, we show that VBP1 enhances the stability of pVHL and facilitates pVHL-mediated ubiquitination of HIF-1α. Furthermore, VBP1 suppresses HIF-1α-induced epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. These findings suggest that VBP1 is a bona fide tumor suppressor protein associated with HIF-1α regulation.
Keywords:
EMT; pVHL; HIF-1α; VBP1; metastasis.
© 2017 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Cytoskeletal Proteins
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HCT116 Cells
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HEK293 Cells
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Mice, Inbred C57BL
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Molecular Chaperones
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Neoplasm Metastasis
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Protein Binding
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RNA Interference
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Ubiquitination
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Von Hippel-Lindau Tumor Suppressor Protein / genetics
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Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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Hypoxia-Inducible Factor 1, alpha Subunit
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Molecular Chaperones
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VBP1 protein, human
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Von Hippel-Lindau Tumor Suppressor Protein
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VHL protein, human