Messenger RNA translation or
protein synthesis, is a fundamental biological process affecting cell growth, survival and proliferation. Initiation is the rate limiting and hence the most regulated step of translation. In eukaryotes, translation initiation is facilitated by multiple
protein factors collectively called eIFs (for eukaryotic translation
initiation factors). The complex consisting of the eIF4 group factors including the
mRNA cap-binding
eIF4E protein, large scaffolding
protein eIF4G and
RNA helicase eIF4A is assisted by the
eIF4B co-factor to unwind local secondary structures and create a ribosome landing pad on
mRNA. Recruitment of the ribosome and augmentation in the
mRNA scanning process culminates in the positioning of the ribosome over the
start codon. Deregulated translational control is believed to play an important role in oncogenic transformation. Indeed, many eIFs are bona fide proto-oncogenes. In many types of human
cancers, eIFs are either overexpressed or ectopically activated by Ras-MAPK and PI3K-mTOR signaling cascades, resulting in increased survival and accelerated proliferation. In this review we will analyze the bulk of data describing
eIF4B and its role in cell survival and proliferation. Recent studies have shown that
eIF4B is phosphorylated and activated by Ras-MAPK and PI3K-mTOR signaling cascades. In addition,
eIF4B regulates translation of proliferative and pro-survival mRNAs. Moreover,
eIF4B depletion in
cancer cells attenuates proliferation, sensitizes them to genotoxic stress-driven apoptosis. Taken together, these findings identify
eIF4B as a potential target for development of anti-
cancer therapies.