Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target
Abstract Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthesis pathway, is responsible for the production of geranylgeranyl pyrophosphate (GGPP). GGPP serves as a substrate for the post‐translational modification (geranylgeranylation) of proteins, including those belo...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.1167 |
| _version_ | 1797306764261064704 |
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| author | Molly E. Muehlebach Sarah A. Holstein |
| author_facet | Molly E. Muehlebach Sarah A. Holstein |
| author_sort | Molly E. Muehlebach |
| collection | DOAJ |
| description | Abstract Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthesis pathway, is responsible for the production of geranylgeranyl pyrophosphate (GGPP). GGPP serves as a substrate for the post‐translational modification (geranylgeranylation) of proteins, including those belonging to the Ras superfamily of small GTPases. These proteins play key roles in signalling pathways, cytoskeletal regulation and intracellular transport, and in the absence of the prenylation modification, cannot properly localise and function. Aberrant expression of GGDPS has been implicated in various human pathologies, including liver disease, type 2 diabetes, pulmonary disease and malignancy. Thus, this enzyme is of particular interest from a therapeutic perspective. Here, we review the physiological function of GGDPS as well as its role in pathophysiological processes. We discuss the current GGDPS inhibitors under development and the therapeutic implications of targeting this enzyme. |
| first_indexed | 2024-03-08T00:46:35Z |
| format | Article |
| id | doaj.art-e86064644ffe4242b518db4ccc729558 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-03-08T00:46:35Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-e86064644ffe4242b518db4ccc7295582024-02-15T08:22:14ZengWileyClinical and Translational Medicine2001-13262023-01-01131n/an/a10.1002/ctm2.1167Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic targetMolly E. Muehlebach0Sarah A. Holstein1Cancer Research Doctoral Program University of Nebraska Medical Center Omaha Nebraska USADepartment of Internal Medicine University of Nebraska Medical Center Omaha Nebraska USAAbstract Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthesis pathway, is responsible for the production of geranylgeranyl pyrophosphate (GGPP). GGPP serves as a substrate for the post‐translational modification (geranylgeranylation) of proteins, including those belonging to the Ras superfamily of small GTPases. These proteins play key roles in signalling pathways, cytoskeletal regulation and intracellular transport, and in the absence of the prenylation modification, cannot properly localise and function. Aberrant expression of GGDPS has been implicated in various human pathologies, including liver disease, type 2 diabetes, pulmonary disease and malignancy. Thus, this enzyme is of particular interest from a therapeutic perspective. Here, we review the physiological function of GGDPS as well as its role in pathophysiological processes. We discuss the current GGDPS inhibitors under development and the therapeutic implications of targeting this enzyme.https://doi.org/10.1002/ctm2.1167geranylgeranyl diphosphate synthasegeranylgeranylationisoprenoid biosynthesis pathwaysmall GTPases |
| spellingShingle | Molly E. Muehlebach Sarah A. Holstein Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target Clinical and Translational Medicine geranylgeranyl diphosphate synthase geranylgeranylation isoprenoid biosynthesis pathway small GTPases |
| title | Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target |
| title_full | Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target |
| title_fullStr | Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target |
| title_full_unstemmed | Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target |
| title_short | Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target |
| title_sort | geranylgeranyl diphosphate synthase role in human health disease and potential therapeutic target |
| topic | geranylgeranyl diphosphate synthase geranylgeranylation isoprenoid biosynthesis pathway small GTPases |
| url | https://doi.org/10.1002/ctm2.1167 |
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