{"doi":"10.1155/2022/2407223","title":"Regulation of Transactivation at C‐TAD Domain of HIF‐1<i>α</i> by Factor‐Inhibiting HIF‐1<i>α</i> (FIH‐1): A Potential Target for Therapeutic Intervention in Cancer","abstract":"<jats:p>Hypoxia‐inducible factor‐1alpha (HIF‐1<jats:italic>α</jats:italic>) is a major transcription factor that adapts to low oxygen homeostasis and regulates the expression of several hypoxic genes, which aid in cancer survival and development. It has recently piqued the interest of translational researchers in the disciplines of cancer sciences. Hypoxia triggers an ample adaptive mechanism mediated via the HIF‐1<jats:italic>α</jats:italic> transcriptional domain. Anaerobic glycolysis, angiogenesis, metastasis, and mitophagy are adaptive mechanisms that support tumor survival by promoting oxygen supply and regulating oxygen demand in hypoxic tumor cells. Throughout this pathway, the factor‐inhibiting HIF‐1<jats:italic>α</jats:italic> is a negative regulator of HIF‐1<jats:italic>α</jats:italic> leading to its hydroxylation at the C‐TAD domain of HIF‐1<jats:italic>α</jats:italic> under normoxia. Thus, hydroxylated HIF‐1<jats:italic>α</jats:italic> is unable to proceed with the transcriptional events due to interference in binding of C‐TAD and CBP/p300. From this review, we can hypothesize that remodeling of FIH‐1 activity is a unique mechanism that decreases the transcriptional activity of HIF‐1<jats:italic>α</jats:italic> and, as a result, all of its hypoxic consequences. Hence, this review manuscript details the depth of knowledge of FIH‐1 on hypoxia‐associated cellular and molecular events, a potential strategy for targeting hypoxia‐induced malignancies.</jats:p>","journal":"Oxidative Medicine and Cellular Longevity","year":2022,"id":678796,"datarank":0.6010999777848708,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":0.0,"self_endowment_contribution":0.6010999777848708,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":809163,"name":"Subhadeep Roy","orcid":"0000-0002-0805-2505","position":1,"is_corresponding":false},{"id":1773535,"name":"Manjari Singh","orcid":"0000-0002-4004-7538","position":2,"is_corresponding":false},{"id":618365,"name":"Gaurav Kaithwas","orcid":"0000-0003-1649-5434","position":3,"is_corresponding":false},{"id":1773534,"name":"Soniya Rani","orcid":"0000-0002-3093-9938","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Regulation of Transactivation at C‐TAD Domain of HIF‐1<i>α</i> by Factor‐Inhibiting HIF‐1<i>α</i> (FIH‐1): A Potential Target for Therapeutic Intervention in Cancer","abstract":"<jats:p>Hypoxia‐inducible factor‐1alpha (HIF‐1<jats:italic>α</jats:italic>) is a major transcription factor that adapts to low oxygen homeostasis and regulates the expression of several hypoxic genes, which aid in cancer survival and development. It has recently piqued the interest of translational researchers in the disciplines of cancer sciences. Hypoxia triggers an ample adaptive mechanism mediated via the HIF‐1<jats:italic>α</jats:italic> transcriptional domain. Anaerobic glycolysis, angiogenesis, metastasis, and mitophagy are adaptive mechanisms that support tumor survival by promoting oxygen supply and regulating oxygen demand in hypoxic tumor cells. Throughout this pathway, the factor‐inhibiting HIF‐1<jats:italic>α</jats:italic> is a negative regulator of HIF‐1<jats:italic>α</jats:italic> leading to its hydroxylation at the C‐TAD domain of HIF‐1<jats:italic>α</jats:italic> under normoxia. Thus, hydroxylated HIF‐1<jats:italic>α</jats:italic> is unable to proceed with the transcriptional events due to interference in binding of C‐TAD and CBP/p300. From this review, we can hypothesize that remodeling of FIH‐1 activity is a unique mechanism that decreases the transcriptional activity of HIF‐1<jats:italic>α</jats:italic> and, as a result, all of its hypoxic consequences. Hence, this review manuscript details the depth of knowledge of FIH‐1 on hypoxia‐associated cellular and molecular events, a potential strategy for targeting hypoxia‐induced malignancies.</jats:p>","is_dataset_classified":null,"base_score":4.007333185232471,"endowment":4.007333185232471,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35592530","pmcid":"PMC9113874","openalex_id":"https://openalex.org/W4280550227","authors":[],"funders":[{"funder_name":"Indian Council of Medical Research","grant_id":"ICMR-SRF 2019-6877","title":null},{"funder_name":"Indian Council of Medical Research","grant_id":"3/2/2/121/2019/NCD-III","title":null}],"total_grants":2,"fwci":4.2714,"citation_percentile":0.96169197,"influential_citations":0,"citation_trend":[{"year":2022,"count":8},{"year":2023,"count":8},{"year":2024,"count":18},{"year":2025,"count":17},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://downloads.hindawi.com/journals/omcl/2022/2407223.pdf","host_type":"journal"},{"url":"https://downloads.hindawi.com/journals/omcl/2022/2407223.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/omcl/2022/2407223.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/omcl/2022/2407223.xml","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1155/2022/2407223","host_type":"publisher"},{"url":"https://doi.org/10.1155/2022/2407223","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35592530","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9113874","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9113874","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9113874?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer, Hypoxia, and Metabolism","RNA modifications and cancer","Mitochondrial Function and Pathology"],"mesh_terms":["Hypoxia","Humans","Mixed Function Oxygenases","Neoplasms","Oxygen","Repressor Proteins","Transcriptional Activation","Hypoxia-Inducible Factor 1, alpha Subunit"],"keywords":["Transactivation","Hypoxia-Inducible Factor 1","HIF1A","Hypoxia-inducible factors","Transcription factor","Angiogenesis","Hypoxia (environmental)","Cancer research","Regulator","Cell biology","Biology","PAS domain","Transcriptional regulation","Tumor progression","Chemistry","Gene","Biochemistry","Oxygen"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T11:26:36.109855Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}