title: Crosstalk between Mdm2, p53 and HIF1-α: distinct responses to oxygen stress and implications for tumour hypoxia.
abstract: The E3 ubiquitin ligase Mdm2 regulates two transcription factors, p53 and HIF1α, which appear to be tailored towards different and specific roles within the cell, the DNA damage and hypoxia responses, respectively. However, evidence increasingly points towards the interplay between these factors being crucial for the regulation of cellular metabolism and survival in times of oxygen stress, which has particular relevance for tumour formation. Mdm2, p53 and HIF1α all respond to hypoxia, and intriguingly, have distinct roles depending on the level of hypoxia. The data from numerous studies across different conditions hint at the interplay between these key factors in cellular homeostasis. Here we try to weave these strands together, to create a picture of the complex tapestry of interactions that demonstrates the importance of the crosstalk between these key regulatory proteins during hypoxia.
authors.affiliation: Department of Functional Genomics and Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC, UMR 7104 CNRS-UdS, U946 INSERM, 1 rue Laurent Fries, BP 10142, 67404, Illkirch Cedex, France.
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Robertson
authors.forename: Kostyantyn
authors.initials: K
authors.lastname: Semenchenko
authors.forename: Bohdan
authors.initials: B
authors.lastname: Wasylyk
mesh_terms: D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D010100:Oxygen