Madan, EshaParker, Taylor M.Pelham, Christopher J.Palma, Antonio M.Peixoto, Maria L.Nagane, MasakiChandaria, AliyaTomás, Ana R.Canas-Marques, RitaHenriques, VanessaGalzerano, AntonioCabral-Teixeira, JoaquimSelvendiran, KaruppaiyahKuppusamy, PeriannanCarvalho, CarlosBeltran, AntonioMoreno, EduardoPati, Uttam K.Gogna, Rajan2020-01-062020-01-062019-11-04Madan, E., Parker, T. M., Pelham, C. J., Palma, A. M., Peixoto, M. L., Nagane, M., … Gogna, R. (2019). HIF-transcribed p53 chaperones HIF-1α. Nucleic acids research, 47(19), 10212–10234. doi:10.1093/nar/gkz766https://hdl.handle.net/1805/21755Chronic hypoxia is associated with a variety of physiological conditions such as rheumatoid arthritis, ischemia/reperfusion injury, stroke, diabetic vasculopathy, epilepsy and cancer. At the molecular level, hypoxia manifests its effects via activation of HIF-dependent transcription. On the other hand, an important transcription factor p53, which controls a myriad of biological functions, is rendered transcriptionally inactive under hypoxic conditions. p53 and HIF-1α are known to share a mysterious relationship and play an ambiguous role in the regulation of hypoxia-induced cellular changes. Here we demonstrate a novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter. In hypoxic cells, this HIF-1α-induced p53 is transcriptionally inefficient but is abundantly available for protein-protein interactions. Further, both WT and MT p53 proteins bind and chaperone HIF-1α to stabilize its binding at its downstream DNA response elements. This p53-induced chaperoning of HIF-1α increases synthesis of HIF-regulated genes and thus the efficiency of hypoxia-induced molecular changes. This basic biology finding has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.en-USCell HypoxiaGene Expression RegulationHypoxia-Inducible Factor 1, alpha SubunitMolecular ChaperonesPromoter Regions, GeneticProtein Interaction MapsResponse ElementsSignal TransductionArticle