Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Oct;19(10):e45947.
doi: 10.15252/embr.201845947. Epub 2018 Sep 17.

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

Affiliations
Review

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

Ashwin Sriram et al. EMBO Rep. 2018 Oct.

Abstract

Recent work has brought to light many different mechanisms of translation initiation that function in cells in parallel to canonical cap-dependent initiation. This has important implications for cancer. Canonical cap-dependent translation initiation is inhibited by many stresses such as hypoxia, nutrient limitation, proteotoxic stress, or genotoxic stress. Since cancer cells are often exposed to these stresses, they rely on alternate modes of translation initiation for protein synthesis and cell growth. Cancer mutations are now being identified in components of the translation machinery and in cis-regulatory elements of mRNAs, which both control translation of cancer-relevant genes. In this review, we provide an overview on the various modes of non-canonical translation initiation, such as leaky scanning, translation re-initiation, ribosome shunting, IRES-dependent translation, and m6A-dependent translation, and then discuss the influence of stress on these different modes of translation. Finally, we present examples of how these modes of translation are dysregulated in cancer cells, allowing them to grow, to proliferate, and to survive, thereby highlighting the importance of translational control in cancer.

Keywords: cancer; stress; translation initiation.

PubMed Disclaimer

Figures

Figure 1
Figure 1. The canonical pathway of eukaryotic translation initiation
The figure shows a schematic representation of the canonical pathway of eukaryotic translation initiation, including the canonical initiation factors and signaling pathways that regulate these initiation factors.
Figure 2
Figure 2. Modes of translation
An overview of the various modes of mRNA translation is shown. For details, please refer to the main text.
Figure 3
Figure 3. Translational dysregulation in cancer
Non‐canonical translational mechanisms found in cancer cells are summarized. Red indicates down‐regulation, and blue indicates up‐regulation.

References

    1. Malys N, McCarthy JE (2011) Translation initiation: variations in the mechanism can be anticipated. Cell Mol Life Sci 68: 991–1003 - PMC - PubMed
    1. Dever TE, Green R (2012) The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb Perspect Biol 4: a013706 - PMC - PubMed
    1. Merrick WC (2010) Eukaryotic protein synthesis: still a mystery. J Biol Chem 285: 21197–21201 - PMC - PubMed
    1. Merrick WC (1992) Mechanism and regulation of eukaryotic protein‐synthesis. Microbiol Rev 56: 291–315 - PMC - PubMed
    1. Hinnebusch AG (2014) The scanning mechanism of eukaryotic translation initiation. Annu Rev Biochem 83: 779–812 - PubMed

Publication types

LinkOut - more resources