The ubiquitin ligase Siah2 and the hypoxia response.
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 1 under oxygen concentration of 2% to 5%, thereby allowing accumulation of hypoxia-inducible factor (HIF)-1alpha, 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.
Nakayama
Koh
K
Burnham Institute for Medical Research, La Jolla, CA, USA. nakayama.mtt@mri.tmd.ac.jp
Qi
Jianfei
J
Ronai
Ze'ev
Z
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D000098563:Seven in Absentia Proteins
D009687:Nuclear Proteins; C533102:Siah2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins