DOI: 10.1126/science.1187532. mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs

mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs

10.1126/science.1187532

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Proliferation Control The protein complex mTORC1, which contains the protein kinase known as mammalian target of rapamycin, is an important regulator of cell proliferation and cell size. Among many targets, mTORC1 phosphorylates the eukaryotic translation initiation factor eIF4E–binding proteins (4E-BPs), thus controlling translation of proteins that regulate proliferation. Dowling et al. (p. 1172 ) used mice lacking expression of the 4E-BPs to show that these proteins contribute to mTORC1's activation of cell proliferation, but are dispensable for the effects of mTORC1 on cell growth. The latter required another mTORC1 target—the ribosomal protein S6 kinase. mTORC1 inhibitors are being explored as potential anticancer agents, and the presence of 4E-BPs was necessary for mTORC1 inhibitors to reduce the number and size of colonies formed by transformed mouse cells.

Bibliography

Dowling, R. J. O., Topisirovic, I., Alain, T., Bidinosti, M., Fonseca, B. D., Petroulakis, E., Wang, X., Larsson, O., Selvaraj, A., Liu, Y., Kozma, S. C., Thomas, G., & Sonenberg, N. (2010). mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs. Science, 328(5982), 1172â1176.

Authors 13

Ryan J. O. Dowling (first)
Ivan Topisirovic (additional)
Tommy Alain (additional)
Michael Bidinosti (additional)
Bruno D. Fonseca (additional)
Emmanuel Petroulakis (additional)
Xiaoshan Wang (additional)
Ola Larsson (additional)
Anand Selvaraj (additional)
Yi Liu (additional)
Sara C. Kozma (additional)
George Thomas (additional)
Nahum Sonenberg (additional)

References 26 Referenced 618

10.1016/j.ccr.2007.05.008
10.1101/gad.1212704
10.1038/371762a0
Choo A. Y., Blenis J., Not all substrates are treated equally: Implications for mTOR, rapamycin-resistance and cancer therapy. Cell Cycle 8, 567 (2009).19197153 (10.4161/cc.8.4.7659) / Cell Cycle / Not all substrates are treated equally: Implications for mTOR, rapamycin-resistance and cancer therapy by Choo A. Y. (2009)
10.1016/S0092-8674(02)00833-4
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Dates

Type	When
Created	15 years, 3 months ago (May 27, 2010, 2:15 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3 a.m.)
Indexed	3 weeks, 4 days ago (Aug. 7, 2025, 5:12 p.m.)
Issued	15 years, 3 months ago (May 28, 2010)
Published	15 years, 3 months ago (May 28, 2010)
Published Print	15 years, 3 months ago (May 28, 2010)

Funders 0

None

BibTeX

@article{Dowling_2010, title={mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs}, volume={328}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1187532}, DOI={10.1126/science.1187532}, number={5982}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Dowling, Ryan J. O. and Topisirovic, Ivan and Alain, Tommy and Bidinosti, Michael and Fonseca, Bruno D. and Petroulakis, Emmanuel and Wang, Xiaoshan and Larsson, Ola and Selvaraj, Anand and Liu, Yi and Kozma, Sara C. and Thomas, George and Sonenberg, Nahum}, year={2010}, month=may, pages={1172–1176} }

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  "abstract": "<jats:title>Proliferation Control</jats:title>\n          <jats:p>\n            The protein complex mTORC1, which contains the protein kinase known as mammalian target of rapamycin, is an important regulator of cell proliferation and cell size. Among many targets, mTORC1 phosphorylates the eukaryotic translation initiation factor eIF4E\u2013binding proteins (4E-BPs), thus controlling translation of proteins that regulate proliferation.\n            <jats:bold>\n              Dowling\n              <jats:italic>et al.</jats:italic>\n            </jats:bold>\n            (p.\n            <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" page=\"1172\" related-article-type=\"in-this-issue\" vol=\"328\" xlink:href=\"10.1126/science.1187532\">1172</jats:related-article>\n            ) used mice lacking expression of the 4E-BPs to show that these proteins contribute to mTORC1's activation of cell proliferation, but are dispensable for the effects of mTORC1 on cell growth. The latter required another mTORC1 target\u2014the ribosomal protein S6 kinase. mTORC1 inhibitors are being explored as potential anticancer agents, and the presence of 4E-BPs was necessary for mTORC1 inhibitors to reduce the number and size of colonies formed by transformed mouse cells.\n          </jats:p>",
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