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

Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
Science (Impact Factor: 33.61). 05/2010; 328(5982):1172-6. DOI: 10.1126/science.1187532
Source: PubMed


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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