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Updated: Jul 29, 2025
Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
Published on: January 16, 2020
Regulation of protein prenylation
Dominik Jung1, Hagen S Bachmann1
1Institute of Pharmacology and Toxicology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany.
Abstract:
Prenyltransferases (PTases) are known to play a role in embryonic development, normal tissue homeostasis and cancer by posttranslationally modifying proteins involved in these processes. They are being discussed as potential drug targets in an increasing number of diseases, ranging from Alzheimer's disease to malaria. Protein prenylation and the development of specific PTase inhibitors (PTIs) have been subject to intense research in recent decades. Recently, the FDA approved lonafarnib, a specific farnesyltransferase inhibitor that acts directly on protein prenylation; and bempedoic acid, an ATP citrate lyase inhibitor that might alter intracellular isoprenoid composition, the relative concentrations of which can exert a decisive influence on protein prenylation. Both drugs represent the first approved agent in their respective substance class. Furthermore, an overwhelming number of processes and proteins that regulate protein prenylation have been identified over the years, many of which have been proposed as molecular targets for pharmacotherapy in their own right. However, certain aspects of protein prenylation, such as the regulation of PTase gene expression or the modulation of PTase activity by phosphorylation, have attracted less attention, despite their reported influence on tumor cell proliferation. Here, we want to summarize the advances regarding our understanding of the regulation of protein prenylation and the potential implications for drug development. Additionally, we want to suggest new lines of investigation that encompass the search for regulatory elements for PTases, especially at the genetic and epigenetic levels.
Insights
Prenyltransferases (PTases) regulate key cellular processes and are emerging drug targets. This review summarizes advances in understanding PTase regulation and explores new therapeutic strategies, including genetic and epigenetic approaches.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Prenyltransferases (PTases) are crucial enzymes involved in protein post-translational modification, impacting embryonic development, tissue homeostasis, and cancer.
- PTases are increasingly recognized as therapeutic targets for diverse diseases, including Alzheimer's and malaria.
- Recent drug approvals, like lonafarnib and bempedoic acid, highlight progress in targeting protein prenylation.
Purpose of the Study:
- To review current understanding of protein prenylation regulation.
- To explore the therapeutic implications of PTase modulation for drug development.
- To identify underexplored regulatory mechanisms and suggest future research directions.
Main Methods:
- Literature review and synthesis of existing research on PTase function and regulation.
- Analysis of recent advancements in PTase inhibitor development and drug approvals.
- Identification of knowledge gaps in PTase gene expression and activity modulation.
Main Results:
- Significant progress has been made in understanding protein prenylation and developing specific inhibitors.
- Approved drugs targeting protein prenylation pathways demonstrate therapeutic potential.
- Regulation of PTase gene expression and activity modulation by phosphorylation remain underexplored areas with potential therapeutic relevance.
Conclusions:
- Further investigation into genetic and epigenetic regulation of PTases is warranted.
- Exploring novel regulatory elements could uncover new therapeutic strategies for diseases involving protein prenylation.
- A comprehensive understanding of PTase regulation is essential for advancing drug development in various medical fields.
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