In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53

Biochem Biophys Res Commun. 2011 Jun 3;409(2):171-6. doi: 10.1016/j.bbrc.2011.04.094. Epub 2011 Apr 24.

Abstract

The cytoplasmic poly (A) binding protein (PABP) interacts with 3' poly (A) tract of eukaryotic mRNA and is important for both translation and stability of mRNA. Previously, we have shown that depletion of PABP by siRNA prevents protein synthesis and consequently leads to cell death through apoptosis. In the present investigation, we studied the mechanism of cell apoptosis. We show that in the absence of PABP, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53. As a result, p53 translocated to the mitochondria to initiate Bax mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Apoptosis / genetics*
  • Cell Nucleus / enzymology*
  • Cytoplasm / metabolism
  • Gene Knockdown Techniques
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism*
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism
  • Phosphorylation
  • Poly(A)-Binding Protein I / genetics
  • Poly(A)-Binding Protein I / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / genetics
  • Serine / genetics
  • Serine / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Poly(A)-Binding Protein I
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Serine
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)