SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

Biochem Biophys Res Commun. 2015 Aug 7;463(4):524-31. doi: 10.1016/j.bbrc.2015.05.069. Epub 2015 May 28.

Abstract

SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells. DJ-1 is both cancer and Parkinson's disease related protein. In the present study we have shown that SG2NA protects DJ-1 from proteasomal degradation in cancer cells. Hence, downregulation of SG2NA reduces DJ-1/Akt colocalization in cancer cells resulting in the reduction of anchorage dependent and independent growth. Thus SG2NA enhances cancer cell survival. Reactive oxygen species enhances SG2NA, DJ-1 and Akt trimerization. Removal of the reactive oxygen species by N-acetyl-cysteine thus reduces cancer cell growth.

Keywords: Akt; Auto-antigen; Cancer; DJ-1; SG2NA; Striatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / physiology*
  • Calmodulin-Binding Proteins / physiology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / physiology*
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oncogene Proteins / metabolism*
  • Peroxiredoxins / metabolism*
  • Protein Deglycase DJ-1
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • Autoantigens
  • Calmodulin-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Reactive Oxygen Species
  • STRN3 protein, human
  • Strn3 protein, mouse
  • Peroxiredoxins
  • Proto-Oncogene Proteins c-akt
  • PARK7 protein, human
  • PARK7 protein, mouse
  • Protein Deglycase DJ-1