Targeting Translation for Treatment of Cancer - A Novel Role for IRES?

Author: Holcik M.

Source: Current Cancer Drug Targets, Volume 4, Number 3, May 2004 , pp. 299-311(13)

Publisher: Bentham Science Publishers

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Abstract:

Protein synthesis plays an important role in the regulation of cell proliferation. While the role of cap-dependent translation in cell transformation has been studied extensively another translation initiation mechanism, internal initiation of cellular mRNAs, emerged recently and is relatively unappreciated and poorly understood. Internal initiation is mediated by IRES elements that are found in the 5' untranslated region (5' UTR) of mRNA. Curiously, several oncogenes, growth factors and proteins involved in the regulation of programmed cell death contain IRES elements in their 5' UTRs. Internal initiation escapes many control mechanisms that regulate cap-dependent translation. In this review I will discuss the data supporting the hypothesis that selective translation of these factors may contribute to the survival of cancer cells under stressful situations, such as lack of nutrients, hypoxia, or therapy-induced DNA damage and contributes to the development and progression of cancer and to the establishment of cancer cells that are resistant to conventional therapies.

Keywords: translation; cancer; ires; irs elements; cap-dependent translation

Document Type: Research article

DOI: http://dx.doi.org/10.2174/1568009043333005

Affiliations: 1: Apoptosis Research Center,Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON K1H 8L1 Canada

Publication date: 2004-05-01

More about this publication?
  • Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
    Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
    As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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