Unique Regulation of Cell Growth and Cell Division by mTORC1 Signaling
Miguel A. Palafox
Mentors: David A. Fruman, Lomon So
Cell growth (increase in mass) and proliferation are fundamental cell biological processes that are coordinated
by the mammalian target of rapamycin (mTOR) signaling network. mTOR integrates a variety of extracellular
signals to control cell growth and division. However, how a vast variety of animal cell types coordinate
growth and proliferation through mTOR is still unclear. To answer this question, we analyzed the function of
two downstream effectors of mTOR; the ribosomal S6 kinases (S6Ks) and the eukaryotic translation initiation
factor 4E (eIF4E)-binding proteins (4E-BPs). Using chemical genetics, we show that acute inhibition of S6Ks
in mouse embryonic fibroblasts (MEFs) results in a decrease in cell size while having no effect on cell
proliferation. In contrast, cell proliferation, but not cell size, was reduced upon induction of a gain-offunction 4E-BP1 mutant in NIH 3T3 fibroblasts. Interestingly, our lab has shown that unlike fibroblast,
primary lymphocytes couple both cell growth and division through the mTOR/4E-BP/eIF4e axis. These
results suggest that multiple mechanisms exist for cells from multicellular organisms in terms of how cell
growth and proliferation is coordinated. Regulation of cell growth and proliferation is often deregulated in
diseases such as cancer. Our results offer implications for understanding the basis of this deregulation in the
context of mTOR signaling that is most often hyperactive in many tumors.