Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-676
Reiling, J H; Doepfner, K T; Hafen, E; Stocker, H (2005). Diet-dependent effects of the Drosophila Mnk1/Mnk2 homolog Lk6 on growth via eIF4E. Current Biology, 15(1):24-30.
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The control of cellular growth is tightly linked to the regulation of protein synthesis. A key function in translation initiation is fulfilled by the 5' cap binding eukaryotic initiation factor 4E (eIF4E), and dysregulation of eIF4E is associated with malignant transformation and tumorigenesis . In mammals, the activity of eIF4E is modulated by phosphorylation at Ser209 by mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) , which themselves are activated by ERK and p38 MAPK in response to mitogens, cytokines or cellular stress . Whether phosphorylation of eIF4E at Ser209 exerts a positive or inhibitory effect on translation efficiency has remained controversial. Here we provide a genetic characterization of the Drosophila homolog of Mnk1/2, Lk6. Lk6 function is dispensable under a high protein diet, consistent with the recent finding that mice lacking both Mnk1 and Mnk2 are not growth-impaired . Interestingly, loss of Lk6 function causes a significant growth reduction when the amino acid content in the diet is reduced. Overexpression of Lk6 also results in growth inhibition in an eIF4E-dependent manner. We propose a model of eIF4E regulation that may reconcile the contradictory findings with regard to the role of phosphorylation by Mnk1/2.
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|Item Type:||Journal Article, refereed|
|Communities & Collections:||07 Faculty of Science > Institute of Zoology (former)|
|Dewey Decimal Classification:||570 Life sciences; biology
590 Animals (Zoology)
|Date:||11 January 2005|
|Deposited On:||11 Feb 2008 12:17|
|Last Modified:||27 Nov 2013 17:29|
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