Regulation of protein prenylation.

Autor: Jung D; Institute of Pharmacology and Toxicology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany., Bachmann HS; Institute of Pharmacology and Toxicology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany. Electronic address: hagen.bachmann@uni-wh.de.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Aug; Vol. 164, pp. 114915. Date of Electronic Publication: 2023 May 24.
DOI: 10.1016/j.biopha.2023.114915
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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