title: Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1α (HIF-1α) during hypoxia.
abstract: A proper cellular adaptation to low oxygen levels is essential for processes such as development, growth, metabolism, and angiogenesis. The response to decrease in oxygen supply, referred to as hypoxia, is also involved in numerous human diseases including cancer, inflammatory conditions, and vascular disease. The hypoxia-inducible factor 1-α (HIF-1α), a key player in the hypoxic response, is kept under stringent regulation. At normoxia, the levels are kept low as a consequence of the efficient degradation by the ubiquitin-proteasome system, and in response to hypoxia, the degradation is blocked and the accumulating HIF-1α promotes a transcriptional response essential for proper adaptation and survival. Here we show that the ubiquitin-specific protease-19 (USP19) interacts with components of the hypoxia pathway including HIF-1α and rescues it from degradation independent of its catalytic activity. In the absence of USP19, cells fail to mount an appropriate response to hypoxia, indicating an important role for this enzyme in normal or pathological conditions.
authors: Departments of Cell and Molecular Biology, Karolinska Institutet, Box 285,171 77 Stockholm, Sweden.
authors: Mikael
authors: M
authors: Altun
authors: Bin
authors: B
authors: Zhao
authors: Kelly
authors: K
authors: Velasco
authors: Haiyin
authors: H
authors: Liu
authors: Gerco
authors: G
authors: Hassink
authors: Julia
authors: J
authors: Paschke
authors: Teresa
authors: T
authors: Pereira
authors: Kristina
authors: K
authors: Lindsten
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D025801:Ubiquitin; D010450:Endopeptidases; C559917:USP19 protein, human; D046988:Proteasome Endopeptidase Complex