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data-entity-id="19140576" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/19140576/Regulation_of_gene_expression_by_hypoxia_Integration_of_the_HIF_transduced_hypoxic_signal_at_the_hypoxia_responsive_element">Regulation of gene expression by hypoxia: Integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34594342" href="https://uci.academia.edu/EricStanbridge">Eric Stanbridge</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Clinica Chimica Acta, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Regulation of gene expression by hypoxia: Integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element","attachmentId":40453842,"attachmentType":"pdf","work_url":"https://www.academia.edu/19140576/Regulation_of_gene_expression_by_hypoxia_Integration_of_the_HIF_transduced_hypoxic_signal_at_the_hypoxia_responsive_element","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/19140576/Regulation_of_gene_expression_by_hypoxia_Integration_of_the_HIF_transduced_hypoxic_signal_at_the_hypoxia_responsive_element"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="100896151" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/100896151/Transcriptional_Response_to_Hypoxia_The_Role_of_HIF_1_Associated_Co_Regulators">Transcriptional Response to Hypoxia: The Role of HIF-1-Associated Co-Regulators</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="69115242" href="https://independent.academia.edu/SimosGeorge">George Simos</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cells</p><p class="ds-related-work--abstract ds2-5-body-sm">The Hypoxia Inducible Factor 1 (HIF-1) plays a major role in the cellular response to hypoxia by regulating the expression of many genes involved in adaptive processes that allow cell survival under low oxygen conditions. Adaptation to the hypoxic tumor micro-environment is also critical for cancer cell proliferation and therefore HIF-1 is also considered a valid therapeutical target. Despite the huge progress in understanding regulation of HIF-1 expression and activity by oxygen levels or oncogenic pathways, the way HIF-1 interacts with chromatin and the transcriptional machinery in order to activate its target genes is still a matter of intense investigation. Recent studies have identified several different HIF-1- and chromatin-associated co-regulators that play important roles in the general transcriptional activity of HIF-1, independent of its expression levels, as well as in the selection of binding sites, promoters and target genes, which, however, often depends on cellular co...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Transcriptional Response to Hypoxia: The Role of HIF-1-Associated Co-Regulators","attachmentId":101587322,"attachmentType":"pdf","work_url":"https://www.academia.edu/100896151/Transcriptional_Response_to_Hypoxia_The_Role_of_HIF_1_Associated_Co_Regulators","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/100896151/Transcriptional_Response_to_Hypoxia_The_Role_of_HIF_1_Associated_Co_Regulators"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="24744858" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN">REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia OPEN</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47951587" href="https://independent.academia.edu/MManresa">M. Manresa</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32999621" href="https://gulbenkian.academia.edu/MiguelCavadas">Miguel Cavadas</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47811246" href="https://kernkracht.academia.edu/MarionMesnieres">Marion Mesnieres</a></div><p class="ds-related-work--abstract ds2-5-body-sm">The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α-(but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response. Hypoxia is a key microenvironmental feature of a range of physiological and pathophysiological conditions including embryonic development, exercise, cancer, ischemia and inflammation 1. Adaptive transcriptional pathways have evolved to help an organism deal with the metabolic threat posed by hypoxia. The best-described transcrip-tional adaptive response in cells is mediated by the hypoxia inducible factor (HIF) signalling pathway, which up-regulates genes which restore oxygen and energy homeostasis 2–4. In normoxia, HIFα is hydroxylated by the prolyl-hydroxylase domain (PHD) family of dioxygenases targeting it for proteosomal degradation 5. This process is reversed in hypoxia and HIFα is stabilized, dimerizes with HIFβ and binds to hypoxia response elements (HRE) in the regulatory regions of target genes 6. HIF drives an adaptive response to hypoxia by promoting the expression of genes including those that regulate erythropoiesis, angiogenesis and glycolysis 6. However in cancer, HIF signalling can be maladaptive and contribute to tumour survival 1. Because of the potentially deleterious effects of over-activation of the HIF pathway, a resolution mechanism is required to resolve its activity in prolonged hypoxia. In the absence of such a resolving mechanism, deleterious consequences such as pathologic angiogenesis and excessive haematocrit due to chronic HIF stabilization may occur 7–9. While several regulators of HIF expression exist, only a few have been shown to be involved in the resolution of the HIF response to hypoxia. PHD2 and PHD3 are, for example, part of an auto-regulatory mechanism, whereby HIF-1α which is stabilized in hypoxia, transcriptionally induces the expression of EGLN1 and EGLN3 genes coding for PHD2 and PHD3 proteins respectively 10–12. The increased expression of the PHD enzymes in turn promotes HIFα hydroxylation, and reduction of its expression in prolonged hypoxia 10. Less is known about the control of HIF1A mRNA stability 11. Interestingly, while HIF-1α protein is transiently up-regulated in hypoxia, the mRNA is frequently found to be repressed 12–15. This transcript attenuation can be conveyed through mRNA destabilization by the protein tristetraprolin in endothelial cells 14 and by miR155 in intestinal epithelial cells 12 .</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia OPEN","attachmentId":45073645,"attachmentType":"pdf","work_url":"https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="12889476" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12889476/Hypoxia_dependent_activation_of_HIF_into_a_transcriptional_regulator">Hypoxia-dependent activation of HIF into a transcriptional regulator</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31869614" href="https://ki.academia.edu/jlruas">Jorge L Ruas</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Seminars in cell & developmental biology</p><p class="ds-related-work--abstract ds2-5-body-sm">Adaptation to conditions of limited oxygen availability (hypoxia) is a critical determinant of cell and tissue viability in several physiological and pathophysiological conditions. The hypoxia-inducible factor (HIF) is an oxygen-sensitive transcriptional activator that, under hypoxia, upregulates the expression of genes involved in the control of glucose metabolism, angiogenesis and cellular proliferation, among others. Activation of HIF to a fully competent transcriptional regulatory protein complex is a multi-step process that involves control of protein stability, subcellular localization, DNA-binding and interaction with transcriptional coregulators. The identity, regulation and hierarchy of interactions between several components of the HIF signal transduction pathway has been the object of intense study over the past decade and will be the subject of this review. Particular emphasis is given to the process of coordinated coactivator recruitment within the cell nucleus. The imp...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-dependent activation of HIF into a transcriptional regulator","attachmentId":45864949,"attachmentType":"pdf","work_url":"https://www.academia.edu/12889476/Hypoxia_dependent_activation_of_HIF_into_a_transcriptional_regulator","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12889476/Hypoxia_dependent_activation_of_HIF_into_a_transcriptional_regulator"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="18959483" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18959483/Oxygen_dependent_regulation_of_hypoxia_inducible_factors_by_prolyl_and_asparaginyl_hydroxylation">Oxygen-dependent regulation of hypoxia-inducible factors by prolyl and asparaginyl hydroxylation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39097420" href="https://adelaide1.academia.edu/DanielPeet">Daniel Peet</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Journal of Biochemistry, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oxygen-dependent regulation of hypoxia-inducible factors by prolyl and asparaginyl hydroxylation","attachmentId":40352456,"attachmentType":"pdf","work_url":"https://www.academia.edu/18959483/Oxygen_dependent_regulation_of_hypoxia_inducible_factors_by_prolyl_and_asparaginyl_hydroxylation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18959483/Oxygen_dependent_regulation_of_hypoxia_inducible_factors_by_prolyl_and_asparaginyl_hydroxylation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="1100208" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/1100208/Hypoxia_inducible_factor_1_HIF_1_promotes_its_degradation_by_induction_of_HIF_%CE%B1_prolyl_4_hydroxylases">Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-α-prolyl-4-hydroxylases</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46634" href="https://utu.academia.edu/PekkaHeikkinen">Pekka Heikkinen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemical …, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">An important regulator involved in oxygen-dependent gene expression is the transcription factor HIF (hypoxia-inducible factor), which is composed of an oxygen-sensitive α-subunit (HIF-1α or HIF-2α) and a constitutively expressed β-subunit. In normoxia, HIF-1α is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenases. The three HIF-modifying human enzymes have been termed prolyl hydroxylase domain containing proteins (PHD1, PHD2 and PHD3). Prolyl hydroxylation leads to pVHL (von-Hippel-Lindau protein)-dependent ubiquitination and rapid proteasomal degradation of HIF-1α. In the present study, we report that human PHD2 and PHD3 are induced by hypoxia in primary and transformed cell lines. In the human osteosarcoma cell line, U2OS, selective suppression of HIF-1α expression by RNA interference resulted in a complete loss of hypoxic induction of PHD2 and PHD3. Induction of PHD2 by hypoxia was lost in pVHL-deficient RCC4 cells. These results suggest that hypoxic induction of PHD2 and PHD3 is critically dependent on HIF-α. Using a VHL capture assay, we demonstrate that HIF-α prolyl-4-hydroxylase capacity of cytoplasmic and nuclear protein extracts was enhanced by prolonged exposure to hypoxia. Degradation of HIF-1α after reoxygenation was accelerated, which demonstrates functional relevance of the present results. We propose a direct, negative regulatory mechanism, which limits accumulation of HIF-1α in hypoxia and leads to accelerated degradation on reoxygenation after long-term hypoxia.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-α-prolyl-4-hydroxylases","attachmentId":51103273,"attachmentType":"pdf","work_url":"https://www.academia.edu/1100208/Hypoxia_inducible_factor_1_HIF_1_promotes_its_degradation_by_induction_of_HIF_%CE%B1_prolyl_4_hydroxylases","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/1100208/Hypoxia_inducible_factor_1_HIF_1_promotes_its_degradation_by_induction_of_HIF_%CE%B1_prolyl_4_hydroxylases"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="56453480" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects">Hypoxia and HIF Signaling: One Axis with Divergent Effects</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47395847" href="https://independent.academia.edu/SimonaFontana4">Simona Fontana</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Molecular Sciences</p><p class="ds-related-work--abstract ds2-5-body-sm">The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia and HIF Signaling: One Axis with Divergent Effects","attachmentId":71833017,"attachmentType":"pdf","work_url":"https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="32020650" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/32020650/Hypoxia_Induced_Gene_Expression_Occurs_Solely_through_the_Action_of_Hypoxia_Inducible_Factor_1_HIF_1_Role_of_Cytoplasmic_Trapping_of_HIF_2_">Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1 (HIF-1 ): Role of Cytoplasmic Trapping of HIF-2 </a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="62009974" href="https://independent.academia.edu/ADadak">A. Dadak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular and Cellular Biology, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1 (HIF-1 ): Role of Cytoplasmic Trapping of HIF-2 ","attachmentId":52286028,"attachmentType":"pdf","work_url":"https://www.academia.edu/32020650/Hypoxia_Induced_Gene_Expression_Occurs_Solely_through_the_Action_of_Hypoxia_Inducible_Factor_1_HIF_1_Role_of_Cytoplasmic_Trapping_of_HIF_2_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/32020650/Hypoxia_Induced_Gene_Expression_Occurs_Solely_through_the_Action_of_Hypoxia_Inducible_Factor_1_HIF_1_Role_of_Cytoplasmic_Trapping_of_HIF_2_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="54034660" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/54034660/Cell_specific_Regulation_of_Hypoxia_inducible_Factor_HIF_1_and_HIF_2_Stabilization_and_Transactivation_in_a_Graded_Oxygen_Environment">Cell-specific Regulation of Hypoxia-inducible Factor (HIF)-1 and HIF-2 Stabilization and Transactivation in a Graded Oxygen Environment</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39191486" href="https://independent.academia.edu/MurrayWhitelaw">Murray Whitelaw</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cell-specific Regulation of Hypoxia-inducible Factor (HIF)-1 and HIF-2 Stabilization and Transactivation in a Graded Oxygen Environment","attachmentId":70593588,"attachmentType":"pdf","work_url":"https://www.academia.edu/54034660/Cell_specific_Regulation_of_Hypoxia_inducible_Factor_HIF_1_and_HIF_2_Stabilization_and_Transactivation_in_a_Graded_Oxygen_Environment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/54034660/Cell_specific_Regulation_of_Hypoxia_inducible_Factor_HIF_1_and_HIF_2_Stabilization_and_Transactivation_in_a_Graded_Oxygen_Environment"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":91238042,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":91238042,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_91238042" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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href="https://www.academia.edu/31547300/HIF_1_is_expressed_in_normoxic_tissue_and_displays_an_organ_specific_regulation_under_systemic_hypoxia">HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="60441002" href="https://independent.academia.edu/DesleyNeil">Desley Neil</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic 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data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/104884074/Hypoxia_responsive_transcription_factors">Hypoxia-responsive transcription factors</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42651569" href="https://independent.academia.edu/EoinCummins">Eoin Cummins</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Pflügers Archiv - European Journal of Physiology, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-responsive transcription factors","attachmentId":104492910,"attachmentType":"pdf","work_url":"https://www.academia.edu/104884074/Hypoxia_responsive_transcription_factors","alternativeTracking":true}"><span 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38055361" href="https://independent.academia.edu/StefanoMandriota">Stefano Mandriota</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The FASEB Journal, 2002</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Widespread, hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs","attachmentId":42053732,"attachmentType":"pdf","work_url":"https://www.academia.edu/18101247/Widespread_hypoxia_inducible_expression_of_HIF_2alpha_in_distinct_cell_populations_of_different_organs","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a 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href="https://weizmann.academia.edu/slava">Vyacheslav Kalchenko</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Blood, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1","attachmentId":42069440,"attachmentType":"pdf","work_url":"https://www.academia.edu/19625977/Transcriptional_regulation_of_vascular_endothelial_cell_responses_to_hypoxia_by_HIF_1","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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ds2-5-body-xs">Scientific reports, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia","attachmentId":86512652,"attachmentType":"pdf","work_url":"https://www.academia.edu/79978178/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/79978178/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="10" data-entity-id="103283874" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/103283874/Hypoxia_inducible_factor_3_is_an_oxygen_dependent_transcription_activator_and_regulates_a_distinct_transcriptional_response_to_hypoxia">Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40849304" href="https://umich.academia.edu/CunmingDuan">Cunming Duan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell reports, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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ds2-5-body-sm ds2-5-body-link" data-author-id="37596470" href="https://independent.academia.edu/michaelzhang42">michael zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Nucleic Acids Research, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia","attachmentId":72395655,"attachmentType":"pdf","work_url":"https://www.academia.edu/57544627/An_integrative_genomics_approach_identifies_Hypoxia_Inducible_Factor_1_HIF_1_target_genes_that_form_the_core_response_to_hypoxia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link 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Metcalf</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The EMBO Journal, 2012</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The updated biology of hypoxia-inducible factor","attachmentId":91391947,"attachmentType":"pdf","work_url":"https://www.academia.edu/87079865/The_updated_biology_of_hypoxia_inducible_factor","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/87079865/The_updated_biology_of_hypoxia_inducible_factor"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="14" data-entity-id="68246294" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/68246294/Roles_Of_HIF_and_2_Oxoglutarate_Dependent_Enzymes_in_Controlling_Gene_Expression_In_Hypoxia">Roles Of HIF and 2-Oxoglutarate Dependent Enzymes in Controlling Gene Expression In Hypoxia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51182548" href="https://independent.academia.edu/SoniaRocha12">Sonia Rocha</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2020</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Roles Of 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