Cell cycle dependence on the mevalonate pathway: Role of cholesterol and non-sterol isoprenoids
[Display omitted] 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...
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| Published in | Biochemical pharmacology Vol. 196; p. 114623 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Inc
01.02.2022
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| Subjects | |
| Online Access | Get full text |
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| Abstract | [Display omitted]
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. |
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| AbstractList | 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. [Display omitted] 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. |
| ArticleNumber | 114623 |
| Author | Lasunción, Miguel A. Gómez-Coronado, Diego Martínez-Botas, Javier Martín-Sánchez, Covadonga Busto, Rebeca |
| Author_xml | – sequence: 1 givenname: Miguel A. surname: Lasunción fullname: Lasunción, Miguel A. email: miguel.a.lasuncion@hrc.es organization: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, Madrid, Spain – sequence: 2 givenname: Javier surname: Martínez-Botas fullname: Martínez-Botas, Javier organization: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, Madrid, Spain – sequence: 3 givenname: Covadonga surname: Martín-Sánchez fullname: Martín-Sánchez, Covadonga organization: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, Madrid, Spain – sequence: 4 givenname: Rebeca orcidid: 0000-0001-9869-4087 surname: Busto fullname: Busto, Rebeca organization: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, Madrid, Spain – sequence: 5 givenname: Diego surname: Gómez-Coronado fullname: Gómez-Coronado, Diego email: diego.gomez@hrc.es organization: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, Madrid, Spain |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34052188$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1158_0008_5472_CAN_22_3450 crossref_primary_10_1093_stmcls_sxac016 crossref_primary_10_3390_toxins15120693 crossref_primary_10_1038_s41467_024_46386_6 crossref_primary_10_3390_ijms24043999 crossref_primary_10_1016_j_intimp_2024_112033 crossref_primary_10_1172_jci_insight_173247 crossref_primary_10_1016_j_micres_2023_127517 crossref_primary_10_1111_ddg_15436 crossref_primary_10_1016_j_cbi_2023_110674 crossref_primary_10_2174_0929866530666230525162545 |
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| Keywords | Intermediate sterols CDK Kv IGF1R TM7SF2 CARC NSDHL TRP PI3K CDC25 TASIN Ld D8D7I A2AR DHCR14 (LBR) SC5DL DOPC Po Lo SREBP GGPS1 HMGCS1 IR SERM LSS 7DHC Lov Mevalonate Kir Scap GPCR MVD mTORC1 Cell proliferation GGPP pRb MVK FPP SRE dNTP BK HMGCR HSD17B7 ACAT2 CRAC LDL Cell cycle PMVK β2AR DPPC FDFT1 FDPS CYP51A1 DHCR24 TRPV1 SC4MOL Cholesterol SQLE TSPO2 APC IDI1/2 Fmev DHCR7 |
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The mevalonate pathway is responsible for the synthesis of isoprenoids, including sterols and other metabolites that are essential for... The mevalonate pathway is responsible for the synthesis of isoprenoids, including sterols and other metabolites that are essential for diverse biological... |
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| SubjectTerms | Animals Cell cycle Cell Cycle - physiology Cell Membrane - drug effects Cell Membrane - metabolism Cell proliferation Cholesterol Cholesterol - metabolism Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Intermediate sterols Mevalonate Mevalonic Acid - metabolism Signal Transduction - drug effects Signal Transduction - physiology Sterols - metabolism Terpenes - metabolism |
| Title | Cell cycle dependence on the mevalonate pathway: Role of cholesterol and non-sterol isoprenoids |
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