Open AccessmRNA Translation and Energy Metabolism in Cancer: The Role of the MAPK and mTORC1 Pathways
Author(s) -
Ivan Topisirović,
Nahum Sonenberg
Publication year - 2011
Publication title -
cold spring harbor symposia on quantitative biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.615
H-Index - 77
eISSN - 1943-4456
pISSN - 0091-7451
DOI - 10.1101/sqb.2011.76.010785
Subject(s) - eif4e , mtorc1 , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , kinase , translation (biology) , biology , carcinogenesis , mapk/erk pathway , signal transduction , protein kinase a , cancer research , chemistry , cancer , biochemistry , messenger rna , genetics , gene
mRNA translation is the most energy-consuming process in the cell and strongly correlates with cellular metabolic activity. Translation and energy metabolism play important roles in homeostatic cell growth and proliferation, and when dysregulated lead to cancer. eIF4E is a key regulator of translation, which promotes oncogenesis by selectively enhancing translation of a subset of tumor-promoting mRNAs (e.g., cyclins and c-myc). PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways, which are strongly implicated in cancer etiology, exert a number of their biological effects by modulating translation. The PI3K/AKT pathway regulates eIF4E function by inactivating the inhibitory 4E-BPs via mTORC1, whereas MAPKs activate MAP kinase signal-integrating kinases 1 and 2, which phosphorylate eIF4E. In addition, AMP-activated protein kinase, which is a central sensor of the cellular energy balance, impairs translation by inhibiting mTORC1. Thus, eIF4E plays a major role in mediating the effects of PI3K/AKT, MAPK, and cellular energetics on mRNA translation.
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