Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes Journal Article

  

Authors:	Rajasekhar, V. K.; Viale, A.; Socci, N. D.; Wiedmann, M.; Hu, X.; Holland, E. C.
Article Title:	Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes
Abstract:	In order to determine the global effects of oncogenic Ras and Akt signaling pathways on translational efficiencies, we compared the gene expression profiles of total cellular mRNA and mRNA associated with polysomes. We found that the immediate effect of Ras and Akt signaling blockade on transcription was relatively modest; however, the profile of mRNA associated with polysomes was substantially altered. These observations indicate that the immediate effect of Ras and Akt signaling regulates the recruitment of specific mRNAs to ribosomes to a far greater extent than they regulate the production of mRNAs by transcriptional effects. The mRNAs most affected are those encoding proteins that regulate growth, transcription regulation, cell to cell interactions, and morphology. These data support a model whereby Ras and Akt signaling primarily lead to cellular transformation by altering the transcriptome and producing a radical shift in the composition of mRNAs associated with actively translating polysomes.
Keywords:	signal transduction; protein kinase b; controlled study; human tissue; human cell; proto-oncogene proteins; nonhuman; brain neoplasms; protein function; protein analysis; animal cell; mouse; animals; cell cycle proteins; mice; cell structure; cluster analysis; gene expression; gene function; tumor cells, cultured; animalia; mice, transgenic; cell transformation, neoplastic; gene expression regulation, neoplastic; transcription regulation; messenger rna; enzyme inhibitors; rna, messenger; oligonucleotide array sequence analysis; cell transformation; protein-serine-threonine kinases; glioblastoma; nucleotide sequence; carcinogenicity; proto-oncogene proteins c-akt; data analysis; growth regulation; rna translation; protein biosynthesis; polysome; polyribosomes; ras protein; ras proteins; cell interaction; unindexed sequence; genetic code; oncogene ras; ribosome; humans; human; article
Journal Title:	Molecular Cell
Volume:	12
Issue:	4
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2003-10-01
Start Page:	889
End Page:	901
Language:	English
DOI:	10.1016/s1097-2765(03)00395-2
PUBMED:	14580340
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0242361561&partnerID=40&md5=a912af259a20faf96a25684e8cf981fb
Notes:	Export Date: 12 September 2014 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/59995