V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

Oncogene. 2014 Mar 20;33(12):1581-9. doi: 10.1038/onc.2013.93. Epub 2013 Apr 8.

Abstract

The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not all, mRNA-encoding ribosomal proteins were seen to be affected by v-erbA. These results suggest that this oncogene could modulate the composition of ribosomes. In the present study, we demonstrate, using two-dimensional difference in gel electrophoresis, that v-erbA-expressing cells have a lower amount of RPL11 associated with the ribosomes. The presence of ribosomes devoid of RPL11 in v-erbA-expressing cells was further confirmed by immunoprecipitation. In order to assess the possible impact of these specialized ribosomes on the translational activity, we analyzed proteomes of either v-erbA or S61G-expressing cells using 2D/mass spectrometry, and identified nine proteins present in differing amounts within these cells. Among these proteins, we focused on HSP70 because of its involvement in erythroid differentiation. Our results indicate that, in v-erbA-expressing cells, hsp70 is not only transcribed but also translated more efficiently, as shown by polyribosome fractionation experiments. We demonstrate here, for the first time, the existence of ribosomes with different protein components, notably ribosomes devoid of RPL11, and a regulation of mRNA translation depending on v-erbA oncogene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Viral
  • Chickens
  • Erythrocytes / cytology*
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics
  • Humans
  • Oncogene Proteins v-erbA / genetics*
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / deficiency*
  • Ribosomal Proteins / genetics
  • Ribosomes / genetics*
  • Ribosomes / metabolism*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription, Genetic

Substances

  • HSP70 Heat-Shock Proteins
  • Oncogene Proteins v-erbA
  • RNA, Messenger
  • Ribosomal Proteins