Epidithiodiketopiperazines Block the Interaction between Hypoxia-inducible Factor-1 (HIF-1 ) and p300 by a Zinc Ejection Mechanism*
نویسندگان
چکیده
Kristina M. Cook, Stephen T. Hilton, Jasmin Mecinović, William B. Motherwell , William D. Figg, and Christopher J. Schofield From NCI, National Institutes of Health, Bethesda, Maryland 20814, the Chemistry Research Laboratory, Department of Chemistry, and the Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom, the Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, London WC1N 1AX, United Kingdom, and the Department of Chemistry, University College London, London WC1H 0AJ, United Kingdom
منابع مشابه
p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1).
HIF-1 (hypoxia-inducible factor-1), a heterodimeric transcription factor comprising HIF-1alpha and HIF-1beta subunits, serves as a key regulator of metabolic adaptation to hypoxia. HIF-1 activity largely increases during hypoxia by attenuating pVHL (von Hippel-Lindau protein)-dependent ubiquitination and subsequent 26 S-proteasomal degradation of HIF-1alpha. Besides HIF-1, the transcription fac...
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The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) expression as paradigmatic markers of HIF-1 activity, we found tha...
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تاریخ انتشار 2009