Abstract
Up to 2% of mammalian proteome is post-translationally modified with isoprenoid lipids. Many of these molecules are key regulators of signaling pathways involved in cellular homeostasis. Appropriate signaling by prenylated proteins requires a combination of correct expression levels, efficient post-translational modification, correct subcellular trafficking and nanolocalisation as well as an appropriately regulated activation/deactivation cycle. Aberrant signaling by prenylated proteins can result from the dysregulation of any of these steps, often contributing to human disease. Owing to the prevalence of dysregulated signaling by prenylated proteins in human disease, considerable research has been undertaken into developing pharmacological inhibitors of protein prenylation. A variety of small molecule farnesyltransferase and geranylgeranyltransferase inhibitors have been developed that have been demonstrated to impair tumor growth in vivo. Additionally the cholesterol lowering drugs known as statins have also been demonstrated to inhibit protein prenylation by preventing the formation of prenylation precursors. This review attempts to summarize the current understanding of protein prenylation and the interplay of processes required for signaling by prenylated proteins. The review also highlights the importance of developing new techniques to assess the effects of current and future therapeutic compounds on global prenylation, so as to accurately explain and predict their effects.
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Nguyen, U.T.T., Goodall, A., Alexandrov, K., Abankwa, D. (2011). Isoprenoid Modifications. In: Vidal, C. (eds) Post-Translational Modifications in Health and Disease. Protein Reviews, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6382-6_1
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