| mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. | |
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MedLine Citation:
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PMID: 20508131 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation and cell size. Hence, mTORC1 is implicated in a large number of human diseases--including diabetes, obesity, heart disease, and cancer--that are characterized by aberrant cell growth and proliferation. Although eukaryotic translation initiation factor 4E-binding proteins (4E-BPs) are critical mediators of mTORC1 function, their precise contribution to mTORC1 signaling and the mechanisms by which they mediate mTORC1 function have remained unclear. We inhibited the mTORC1 pathway in cells lacking 4E-BPs and analyzed the effects on cell size, cell proliferation, and cell cycle progression. Although the 4E-BPs had no effect on cell size, they inhibited cell proliferation by selectively inhibiting the translation of messenger RNAs that encode proliferation-promoting proteins and proteins involved in cell cycle progression. Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation. |
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Authors:
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Ryan J O Dowling; Ivan Topisirovic; Tommy Alain; Michael Bidinosti; Bruno D Fonseca; Emmanuel Petroulakis; Xiaoshan Wang; Ola Larsson; Anand Selvaraj; Yi Liu; Sara C Kozma; George Thomas; Nahum Sonenberg |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 328 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-28 Completed Date: 2010-06-08 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1172-6 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / genetics, metabolism* Cell Cycle Cell Enlargement* Cell Line Cell Proliferation* Cell Size Cell Survival Eukaryotic Initiation Factors / genetics, metabolism* Humans Mice Mice, Knockout Phosphoproteins / genetics, metabolism* Phosphorylation Protein Biosynthesis RNA, Messenger / genetics, metabolism Ribosomal Protein S6 Kinases / metabolism Signal Transduction Sirolimus / pharmacology Transcription Factors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P50 NS057531/NS/NINDS NIH HHS; P50 NS057531-01A2/NS/NINDS NIH HHS; R01 DK73802/DK/NIDDK NIH HHS; U01 CA84292-06/CA/NCI NIH HHS; //Canadian Institutes of Health Research; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Eif4ebp1 protein, mouse; 0/Eif4ebp2 protein, mouse; 0/Eukaryotic Initiation Factors; 0/Phosphoproteins; 0/RNA, Messenger; 0/Transcription Factors; 0/mTORC1 complex, human; 0/mTORC1 complex, mouse; 53123-88-9/Sirolimus; EC 2.7.11.1/Ribosomal Protein S6 Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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