Original Paper

Cell Biochemistry and Biophysics

, Volume 67, Issue 1, pp 15-24

First online:

Regulators and Effectors of Siah Ubiquitin Ligases

  • Jianfei QiAffiliated withSignal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute
  • , Hyungsoo KimAffiliated withSignal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute
  • , Marzia ScortegagnaAffiliated withSignal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute
  • , Ze’ev A. RonaiAffiliated withSignal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute Email author 

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Abstract

The Siah ubiquitin ligases are members of the RING finger E3 ligases. The Siah E3s are conserved from fly to mammals. Primarily implicated in cellular stress responses, Siah ligases play a key role in hypoxia, through the regulation of HIF-1α transcription stability and activity. Concomitantly, physiological conditions associated with varying oxygen tension often highlight the importance of Siah, as seen in cancer and neurodegenerative disorders. Notably, recent studies also point to the role of these ligases in fundamental processes including DNA damage response, cellular organization and polarity. This review summarizes the current understanding of upstream regulators and downstream effectors of Siah.

Keywords

Siah1 Siah2 Ubiquitin ligase Hypoxia Stress signaling DNA damage