C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation

  title={C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation},
  author={Andrew C.R. Epstein and Jonathan Gleadle and Luke A. McNeill and Kirsty S. Hewitson and John F. O'Rourke and David R Mole and Mridul Mukherji and Eric Metzen and Michael I. Wilson and Anu Dhanda and Y A Tian and Norma Masson and Donald L. Hamilton and Panu Jaakkola and Robert J. Barstead and Jonathan Hodgkin and Patrick Henry Maxwell and Christopher W Pugh and Christopher J. Schofield and Peter J Ratcliffe},
HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. Recent studies have defined posttranslational modification by prolyl hydroxylation as a key regulatory event that targets HIF-alpha subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Here, we define a conserved HIF-VHL-prolyl hydroxylase pathway in C. elegans, and use a genetic approach to identify EGL-9 as a dioxygenase that regulates HIF by prolyl hydroxylation. In… CONTINUE READING
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