Skip to main content

Normoxic destabilization of ATF-4 depends on proteasomal degradation

Buy Article:

$43.00 plus tax (Refund Policy)

Abstract Aim: 

Hypoxia-inducible gene expression is an important physiological adaptive mechanism in response to a decreased oxygen supply. We have recently described an oxygen- and prolyl-4-hydroxylase (PHD)3-dependent stabilization of the activating transcription factor 4 (ATF-4). The aim of the present study was to examine if the normoxic destabilization of ATF-4 is regulated by oxygen-dependent proteasomal degradation. Methods: 

We determined poly-ubiquitination of ATF-4 in normoxia compared to hypoxia by immunoprecipitation and immunoblots. Furthermore, we analysed the expression of the ATF-4 target gene GADD153 as a function of oxygen concentration. Results: 

ATF-4 protein levels were not detectable in normoxia. Normoxic degradation correlated with an oxygen-dependent poly-ubiquitination of ATF-4, which was hindered by hypoxic incubation of the cells. As a result of hypoxia, GADD153 was expressed. The hypoxic GADD153 expression was attenuated or increased by transfecting the cells with ATF-4 siRNA or PHD3 siRNA respectively. Conclusion: 

Our results demonstrate the involvement of oxygen-dependent proteasomal degradation of ATF-4 in the hypoxia-induced expression of GADD153. Taken together, hypoxia/PHD3-regulated stabilization of ATF-4 by hindering oxygen-dependent degradation may play a critical role in linking cell fate decisions to oxygen availability.
No References
No Citations
No Supplementary Data
No Data/Media
No Metrics

Keywords: ATF-4; hypoxia; proteasome; β-TRCP

Document Type: Research Article

Publication date: 2010-04-01

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more