The ubiquitin ligase Siah2 and the hypoxia response

Koh Nakayama, Jianfei Qi, Ze'ev Ronai

Research output: Contribution to journalShort surveypeer-review

96 Scopus citations


Growing evidence indicates that ubiquitin ligases play a critical role in the hypoxia response. Among them, Siah2, a RING finger ligase, is an important regulator of pathways activated under hypoxia. Siah2 regulates prolyl hydroxylases PHD3 and 1under oxygen concentration of 2% to 5%, thereby allowing accumulation of hypoxia-inducible factor (HIF)-1α, a master regulator of the hypoxia response within the range of physiological normoxic to mild hypoxic conditions. Growing evidence also indicates an important function for Siah2 in tumor development and progression based on pancreatic cancer, mammary tumor, and melanoma mouse models. This review summarizes our current understanding of Siah2 regulation and function with emphasis on hypoxia and tumorigenesis.

Original languageEnglish
Pages (from-to)443-451
Number of pages9
JournalMolecular Cancer Research
Issue number4
StatePublished - 1 Apr 2009
Externally publishedYes


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