Postgenomic global analysis of translational control induced by oncogenic signaling.
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.
Rajasekhar
Vinagolu K
VK
Department of Surgery (Neurosurgery), Neurology, Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. vinagolr@mskcc.org
Holland
Eric C
EC
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D020413:3' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D018631:ras Proteins