Document Detail

The Rb-family protein p107 inhibits translation by a PDK1-dependent mechanism.
MedLine Citation:
PMID:  12420226     Owner:  NLM     Status:  MEDLINE    
The Rb family of proteins, which consists of Rb, p107 and p130, are critical regulators of cell proliferation. In addition to their inhibitory effects on cell cycle progression, Rb-family proteins repress transcription by RNA polymerases I and III, and may therefore restrain cell growth. However, it is not known if Rb, p107 or p130 have direct effects on protein synthesis. Here we report that ectopic expression of p107 in rat fibroblasts markedly attenuates the stimulation of mRNA translation and global protein synthesis by serum growth factors. This effect is associated with a reduction in the phosphorylation and activation of the serine-threonine kinases Akt1 and p70 S6 kinase (S6K1), two downstream targets of phosphoinositide-dependent kinase 1 (PDK1). We show that overexpression of p107 interferes with the recruitment of PDK1 to the plasma membrane in response to growth factors. Overexpression of PDK1 restores the defect in translation elicited by p107. These results suggest that p107 restricts cell growth by interfering with the phosphoinositide 3-kinase (PI3K) signaling pathway.
Constantin Makris; Laure Voisin; Edith Giasson; Christopher Tudan; David R Kaplan; Sylvain Meloche
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  21     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-06     Completed Date:  2002-12-12     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  7891-6     Citation Subset:  IM    
Institut de recherches cliniques de Montréal and Department of Pharmacology, University of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada.
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MeSH Terms
Amino Acid Motifs
Cell Division
Cell Line / metabolism
Culture Media, Serum-Free / pharmacology
Fibroblasts / metabolism
Genetic Complementation Test
Nuclear Proteins / genetics,  physiology*
Phosphatidylinositol 3-Kinases / physiology
Protein Biosynthesis / physiology*
Protein Processing, Post-Translational
Protein Transport
Protein-Serine-Threonine Kinases / chemistry,  metabolism,  physiology*
Proto-Oncogene Proteins*
Proto-Oncogene Proteins c-akt
RNA, Messenger / biosynthesis
Recombinant Fusion Proteins / physiology
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction
Subcellular Fractions / enzymology
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Recombinant Fusion Proteins; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC protein, rat; EC Kinases; EC Proteins c-akt; EC Protein S6 Kinases, 70-kDa; EC protein S6 kinase, 70kD, polypeptide 1

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