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| Status |
Public on Apr 01, 2008 |
| Title |
eIF4GI Links Nutrient Sensing by mTOR to Cell Proliferation and Inhibition of Autophagy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Translation initiation factors have complex functions in cells which are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient-starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation and bioenergetics were selectively inhibited by reduction of eIF4GI, whereas mRNAs encoding proliferation inhibitors and catabolic pathway factors were increased. Depletion or over-expression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy and release tumor cells from control by nutrient sensing.
Global regulation of transcription and polysomal association in eIF4GI-silenced cells.
Keywords: Gene Silencing
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| Overall design |
Two sets of experiments are presented. First, overall transcriptome changes were determined for control or eIF4GI silenced cells. Next, mRNAs associated with polysomes were compared between control and eIF4GI silenced cells.
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| Contributor(s) |
Ramirez-Valle F, Braunstein S, Zavadil J, Fermenti SC, Schneider RJ |
| Citation(s) |
18426977 |
| |
| Submission date |
Apr 01, 2008 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Robert J Schneider |
| E-mail(s) |
robert.schneider@nyumc.org
|
| Phone |
+1-212-263-6006
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| Organization name |
NYU School of Medicine
|
| Department |
Microbiology
|
| Street address |
550 First Ave, MSB 238
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (12)
|
| GSM278478 |
human_MCF10A_siRNA-eIF4GI_polysomal RNA_R1 |
| GSM278479 |
human_MCF10A_siRNA-eIF4GI_polysomal RNA_R2 |
| GSM278480 |
human_MCF10A_siRNA-eIF4GI_polysomal RNA_R3 |
| GSM278481 |
human_MCF10A_siRNA-control_polysomal RNA_R1 |
| GSM278482 |
human_MCF10A_siRNA-control_polysomal RNA_R2 |
| GSM278483 |
human_MCF10A_siRNA-control_polysomal RNA_R3 |
| GSM278484 |
human_MCF10A_siRNA-eIF4GI_total RNA_R1 |
| GSM278485 |
human_MCF10A_siRNA-eIF4GI_total RNA_R2 |
| GSM278486 |
human_MCF10A_siRNA-eIF4GI_total RNA_R3 |
| GSM278487 |
human_MCF10A_siRNA-control_total RNA_R1 |
| GSM278488 |
human_MCF10A_siRNA-control_total RNA_R2 |
| GSM278489 |
human_MCF10A_siRNA-control_total RNA_R3 |
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| Relations |
| BioProject |
PRJNA107097 |
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