The c10orf10 gene product is a new link between oxidative stress and autophagy

Marcus W. Stepp, Rodney J. Folz, Jerry Yu, Igor N. Zelko

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The human c10orf10 gene product, also known as decidual protein induced by progesterone (DEPP), is known to be differentially regulated in mouse tissues in response to hypoxia and oxidative stress, however its biological function remains unknown. We found that mice lacking extracellular superoxide dismutase (EC-SOD) show attenuated expression of DEPP in response to acute hypoxia. DEPP mRNA levels, as well as the activity of a reporter gene expressed under the control of the DEPP 5'-flanking region, were significantly upregulated in Hep3B and Vero cells overexpressing EC-SOD. Subcellular fractionation and immunofluorescent microscopy indicated that overexpressed DEPP is co-localized with both protein aggregates and aggresomes. Further biochemical characterization indicates that DEPP protein is unstable and undergoes rapid degradation. Inhibition of proteasome activities significantly increases DEPP protein levels in soluble and insoluble cytosolic fractions. Attenuation of autophagosomal activity by 3-methyladenine increases DEPP protein levels while activation of autophagy by rapamycin reduced DEPP protein levels. In addition, ectopic overexpression of DEPP leads to autophagy activation, while silencing of DEPP attenuates autophagy. Collectively, these results indicate that DEPP is a major hypoxia-inducible gene involved in the activation of autophagy and whose expression is regulated by oxidative stress.

Original languageEnglish (US)
Pages (from-to)1076-1088
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Aggresomes
  • Autophagy
  • DEPP
  • Extracellular superoxide dismutase
  • Hypoxia
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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