Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types. Data on mice models have demonstrated that eIF6 cytoplasmic activity is rate-limiting for Myc-induced lymphomagenesis. In spite of this, eIF6 is neither transcriptionally regulated by Myc, nor post-transcriptionally regulated by mTOR. eIF6 stimulates a glycolytic and fatty acid synthesis program necessary for tumor growth. eIF6 increases the translation of transcription factors necessary for lipogenesis, such as CEBP/β, ATF4 and CEBP/δ. Insulin stimulation leads to an increase in translation and fat synthesis blunted by eIF6 deficiency. Paradoxycally, long-term inhibition of eIF6 activity increases insulin sensitivity, suggesting that the translational activation observed upon insulin and growth factors stimulation acts as a feed-forward mechanism regulating lipid synthesis. The data on the role that eIF6 plays in cancer and in insulin sensitivity make it a tempting pharmacological target for cancers and metabolic diseases. We speculate that eIF6 inhibition will be particularly effective especially when mTOR sensitivity to rapamycin is abrogated by RAS mutations.
-
Cover Image
Cover Image
Views of the Fc region of human immunoglobulin A (IgA) with interaction sites for key host receptors highlighted in the upper images, and those for bacterial IgA binding proteins in the lower ones. The remarkable co-localisation of these sites illustrates how various bacterial pathogens have co-opted sites on immunoglobulins as an effective means to block the elimination mechanisms which immunoglobulins normally trigger. See pp. 1651–1658 for further information. Image provided by J. Woof.
Translational control by mTOR-independent routes: how eIF6 organizes metabolism
Annarita Miluzio, Sara Ricciardi, Nicola Manfrini, Roberta Alfieri, Stefania Oliveto, Daniela Brina, Stefano Biffo; Translational control by mTOR-independent routes: how eIF6 organizes metabolism. Biochem Soc Trans 15 December 2016; 44 (6): 1667–1673. doi: https://doi.org/10.1042/BST20160179
Download citation file:
Sign in
Sign in to your personal account
Captcha Validation Error. Please try again.