Siah: New players in the cellular response to hypoxia

Koh Nakayama, Ze'ev Ronai

Research output: Contribution to journalShort surveypeer-review

38 Scopus citations


Prolyl-hydroxylation of HIF-1α is a prerequisite for pVHL binding to HIF-1α, which results in degradation of HIF-1α by the ubiquitin-proteasome pathway. Hydroxylation of HIF-1α is mediated by the family of prolyl-hydroxylase proteins (PHD). In hypoxia, HIF-1α is stabilized as a result of inhibition of HIF-1α hydroxylation, which in part is achieved by decreased activity of PHD enzymes at very low oxygen concentrations. We recently demonstrated that in hypoxia the stability of 2 of 3 PHDs (1 and 3) is regulated by the E3 ligases Siah1/2. Consequently, in hypoxia Siah determines the availability of PHD1/3, which otherwise modify HIF-1α to enable its association-dependent degradation by pVHL. These findings define a newly discovered layer in the regulation of HIF-1α in hypoxia. The roles of Siah activities in hypoxia responses are discussed.

Original languageEnglish
Pages (from-to)1345-1347
Number of pages3
JournalCell Cycle
Issue number11
StatePublished - Nov 2004


  • HIF-1α
  • Hypoxia
  • Prolyl-hydroxylase
  • RING-finger protein
  • Siah
  • Ubiquitin ligase


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