Postgenomic global analysis of translational control induced by oncogenic signaling

Oncogene. 2004 Apr 19;23(18):3248-64. doi: 10.1038/sj.onc.1207546.

Abstract

It is commonly assumed that developmental and oncogenic signaling achieve their phenotypic effects primarily by directly regulating the transcriptional profile of cells. However, there is growing evidence that the direct effect on transcription may be overshadowed by differential effects on the translational efficiency of specific existing mRNA species. Global analysis of this effect using microarrays indicates that this mechanism of controlling protein production provides a highly specific, robust, and rapid response to oncogenic and developmental stimuli. The mRNAs so affected encode proteins involved in cell-cell interaction, signal transduction, and growth control. Furthermore, a large number of transcription factors capable of secondarily rearranging the transcriptional profile of the cell are controlled at this level as well. To what degree this translational control is either necessary or sufficient for tumor formation or maintenance remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 3' Untranslated Regions / metabolism
  • Animals
  • Eukaryotic Initiation Factor-4E / physiology
  • Gene Expression Profiling
  • Humans
  • Neoplasms / etiology*
  • Neoplasms / genetics
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Biosynthesis*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • Ribosomes / metabolism
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / physiology
  • ras Proteins / physiology

Substances

  • 3' Untranslated Regions
  • Eukaryotic Initiation Factor-4E
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • ras Proteins