Article

The cancerous translation apparatus

School of Medicine and Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158-3110, USA.
Current opinion in genetics & development (Impact Factor: 7.57). 05/2011; 21(4):474-83. DOI: 10.1016/j.gde.2011.03.007
Source: PubMed

ABSTRACT

Deregulations in translational control are critical features of cancer initiation and progression. Activation of key oncogenic pathways promotes rapid and dramatic translational reprogramming, not simply by increasing overall protein synthesis, but also by modulating specific mRNA networks that promote cellular transformation. Additionally, ribosomopathies caused by mutations in ribosome components alter translational regulation leading to specific pathological features, including cancer susceptibility. Exciting advances in our understanding of translational control in cancer have illuminated a striking specificity innate to the translational apparatus. Characterizing this specificity will provide novel insights into how cells normally utilize translational control to modulate gene expression, how it is deregulated in cancer, and how these processes can be targeted to develop new cancer therapies.

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Available from: ncbi.nlm.nih.gov
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    • "Using X-DC as a model, we showed that rRNA hypopseudouridylation decreases the affinity of ribosomes for at least two classes of RNA ligands, internal ribosomal entry signals (IRES) and tRNAs [30]. While this leads to decreased expression of IRES containing mRNAs (emerging as an important driver of cancer [31]), this biochemical defect also renders tRNAs more likely to slip at -1 PRF signals. The effects of X-DC associated mutations on -1 PRF and gene expression is currently a topic of intense research. "
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    • "As these cells rely exclusively in CK1 for growth and survival (Rosenberg et al., 2015), these findings indicate that the CK1- hLtv1 circuit is operational and essential for ribosome assembly in higher eukaryotes, which is consistent with previous findings that demonstrate a role for CK1/CK1 in 40S ribosome maturation (Zemp et al., 2014). Our findings are also consistent with previous observations that the ribosome assembly pathway is up-regulated in all cancers, which require marked increases in protein synthesis (Ruggero and Pandolfi, 2003; Stumpf and Ruggero, 2011). Finally, our findings validate the ribosome biogenesis machinery as an attractive and novel target for anticancer therapeutics. "
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    • "Many signaling pathways converge on components of the translational apparatus to regulate their function, particularly at the level of eukaryotic translation initiation factors (eIFs), such as eIF4E and eIF2α [2] [6]. Translational control is a crucial component of cancer development and progression, as it directs both global protein synthesis and the selective translation of mRNAs involved in tumor cell growth, survival and proliferation [7] [8] [9]. Consistent with this, many components of the translational machinery were reported to be amplified or overexpressed in human malignancies, including eIF4E, eIF4G, eIF4A and several eIF3 isoforms (Table 1) [9]. "
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