Rho activity can alter the translation of p27 mRNA and is important for RasV12-induced transformation in a manner dependent on p27 status Journal Article
| Authors: | Vidal, A.; Sean Millard, S.; Miller, J. P.; Koff, A. |
| Article Title: | Rho activity can alter the translation of p27 mRNA and is important for RasV12-induced transformation in a manner dependent on p27 status |
| Abstract: | The amount of p27Kip1 establishes a threshold to which G1 cyclin-cyclin-dependent kinase complexes must surpass prior to cells progressing into S-phase. The amount of p27 is greatest in G0 cells, intermediate in G1 cells, and lowest in S-phase cells. However, there is little known regarding the pathways and mechanisms controlling p27 accumulation in G0 cells. We report that inhibition of Rho, by either lovastatin or C3 exoenzyme, can increase the translational efficiency of p27 mRNA. Similar pharmacologic inhibition of the phosphatidylinositol 3-kinase, the S6 kinase, and the Mek1 kinase pathways all fail to increase translational efficiency in MDA468 cells. This Rho-responsive element lies within a 300-nucleotide region at the 3′-end of the mRNA. By supporting the significance of this signaling pathway to Rho function, we showed that the suppression of RasV12 transformation by RhoAN19 is blocked in p27-/-cells. In contrast this activity is not blocked in Rb-/- or p16-/-cells. The resistance of p27-/- cells to RhoAN19 is not associated with a failure of RhoAN19 to accumulate to amounts sufficient to block Rho activity as measured by the organization of actin stress fibers. Together these results indicate a link between Rho and p27. |
| Keywords: | signal transduction; s6 kinase; controlled study; unclassified drug; nonhuman; animal cell; mouse; animals; cell cycle proteins; mice; actin; cells, cultured; cell cycle; cell cycle s phase; complex formation; enzyme inhibition; embryo; dose-response relationship, drug; tumor cells, cultured; transfection; phosphatidylinositol 3 kinase; time factors; animalia; rna; messenger rna; rna, messenger; cell transformation; protein-serine-threonine kinases; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; 1-phosphatidylinositol 3-kinase; immunoblotting; fibroblasts; mitogen activated protein kinase 1; rna translation; protein biosynthesis; translation; plasmids; ras protein; 3' untranslated region; ras proteins; cycline; cyclin dependent kinase; biochemistry; dna responsive element; mitogen-activated protein kinase kinases; cell cycle g1 phase; rho gtp-binding proteins; map kinase kinase 1; s phase; enzymes; cell cycle g0 phase; cell transformation, viral; 3t3 cells; 3' untranslated regions; nucleotide; enzyme; rho factor; mevinolin; botulinum toxins; stress fiber; adp ribose transferases; ribosomal protein s6 kinases; lovastatin; humans; priority journal; article; exoenzyme c3 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 277 |
| Issue: | 19 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2002-05-10 |
| Start Page: | 16433 |
| End Page: | 16440 |
| Language: | English |
| DOI: | 10.1074/jbc.M112090200 |
| PUBMED: | 11875067 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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