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eIF3d Regulates the mTOR Pathway, Cell Growth and Proliferation
Author(s) -
Binder Pablo,
Whitmarsh Alan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb87
Subject(s) - mtorc2 , mtorc1 , pi3k/akt/mtor pathway , microbiology and biotechnology , regulator , cell growth , protein kinase b , phosphorylation , biology , signal transduction , p70 s6 kinase 1 , chemistry , biochemistry , gene
The protein kinase mTOR participates in the response to environmental cues by regulating cell growth and proliferation. As a central regulator of cell metabolism, it has gained attention due to its role in many human diseases, including cancer and diabetes. Thus, great efforts are being made to understand signaling via the mTOR pathway as it represents an interesting pharmacological target. The discovery that one of the two major mTOR‐containing complexes, mTORC2, is a key regulator of the activities of the AGC family kinases Akt, PKC and SGK1, and is involved in cellular processes such as proliferation and cell survival, has stimulated the study of its activation and regulation. Sin1 is a core component of mTORC2 and may act as a scaffold to recruit substrates to the complex. eIF3d, a non‐core component of the eIF3 translational initiation complex, has been identified as a novel Sin1 interacting protein. eIF3d co‐precipitates with Sin1 from cells, however, the biological consequences of this interaction remain unclear. In Hela cells, knockdown of eIF3d expression causes a decrease in the phosphorylation of the mTORC2 targets AKT and PKC on their turn motif sites, but also leads to a significant increase in the phosphorylation and activation of the mTORC1 target S6K. This suggests that eIF3d is a regulator of both mTORC1 and mTORC2 signaling. Reduced expression of eIF3d also leads to an increase in cell size, decreased cell proliferation and impairment of cell cycle progression. Thus eIF3d appears to be a regulator of cell size and proliferation, possibly through the modulation of the mTORC1 and mTORC2 pathways.