Cell cycle dependence on the mevalonate pathway: Role of cholesterol and non-sterol isoprenoids
| Autor: | Diego Gómez-Coronado, Rebeca Busto, Miguel A. Lasunción, Covadonga Martín-Sánchez, Javier Martínez-Botas |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell division Cell Mevalonic Acid Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Pharmacology Chemistry Cholesterol Cell growth Terpenes Cell Cycle Cell Membrane Cell cycle Sterol Cell biology Sterols 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell lipids (amino acids peptides and proteins) Mevalonate pathway Hydroxymethylglutaryl-CoA Reductase Inhibitors Signal Transduction |
| Zdroj: | Biochemical pharmacology. 196 |
| ISSN: | 1873-2968 |
| Popis: | The mevalonate pathway is responsible for the synthesis of isoprenoids, including sterols and other metabolites that are essential for diverse biological functions. Cholesterol, the main sterol in mammals, and non-sterol isoprenoids are in high demand by rapidly dividing cells. As evidence of its importance, many cell signaling pathways converge on the mevalonate pathway and these include those involved in proliferation, tumor-promotion, and tumor-suppression. As well as being a fundamental building block of cell membranes, cholesterol plays a key role in maintaining their lipid organization and biophysical properties, and it is crucial for the function of proteins located in the plasma membrane. Importantly, cholesterol and other mevalonate derivatives are essential for cell cycle progression, and their deficiency blocks different steps in the cycle. Furthermore, the accumulation of non-isoprenoid mevalonate derivatives can cause DNA replication stress. Identification of the mechanisms underlying the effects of cholesterol and other mevalonate derivatives on cell cycle progression may be useful in the search for new inhibitors, or the repurposing of preexisting cholesterol biosynthesis inhibitors to target cancer cell division. In this review, we discuss the dependence of cell division on an active mevalonate pathway and the role of different mevalonate derivatives in cell cycle progression. |
| Databáze: | OpenAIRE |
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