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Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development
Decreasing the levels of certain proteins has been shown to be important for controlling cancer but it is currently unknown whether proteins could potentially be targeted by the inhibiting of protein synthesis. Under this circumstance, targeting protein translation could preferentially affect certai...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998919/ https://www.ncbi.nlm.nih.gov/pubmed/35408842 http://dx.doi.org/10.3390/ijms23073481 |
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author | Dinavahi, Saketh S. Chen, Yu-Chi Gowda, Raghavendra Dhanyamraju, Pavan Kumar Punnath, Kishore Desai, Dhimant Berg, Arthur Kimball, Scot R. Amin, Shantu Yang, Jin-Ming Robertson, Gavin P. |
author_facet | Dinavahi, Saketh S. Chen, Yu-Chi Gowda, Raghavendra Dhanyamraju, Pavan Kumar Punnath, Kishore Desai, Dhimant Berg, Arthur Kimball, Scot R. Amin, Shantu Yang, Jin-Ming Robertson, Gavin P. |
author_sort | Dinavahi, Saketh S. |
collection | PubMed |
description | Decreasing the levels of certain proteins has been shown to be important for controlling cancer but it is currently unknown whether proteins could potentially be targeted by the inhibiting of protein synthesis. Under this circumstance, targeting protein translation could preferentially affect certain pathways, which could then be of therapeutic advantage when treating cancer. In this report, eukaryotic elongation factor-2 kinase (EEF2K), which is involved in protein translation, was shown to regulate cholesterol metabolism. Targeting EEF2K inhibited key parts of the cholesterol pathway in cancer cells, which could be rescued by the addition of exogenous cholesterol, suggesting that it is a potentially important pathway modulated by targeting this process. Specifically, targeting EEF2K significantly suppressed tumour cell growth by blocking mRNA translation of the cholesterol biosynthesis transcription factor, sterol regulatory element-binding protein (SREBP) 2, and the proteins it regulates. The process could be rescued by the addition of LDL cholesterol taken into the cells via non-receptor-mediated-uptake, which negated the need for SREBP2 protein. Thus, the levels of SREBP2 needed for cholesterol metabolism in cancer cells are therapeutically vulnerable by targeting protein translation. This is the first report to suggest that targeting EEF2K can be used to modulate cholesterol metabolism to treat cancer. |
format | Online Article Text |
id | pubmed-8998919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89989192022-04-12 Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development Dinavahi, Saketh S. Chen, Yu-Chi Gowda, Raghavendra Dhanyamraju, Pavan Kumar Punnath, Kishore Desai, Dhimant Berg, Arthur Kimball, Scot R. Amin, Shantu Yang, Jin-Ming Robertson, Gavin P. Int J Mol Sci Article Decreasing the levels of certain proteins has been shown to be important for controlling cancer but it is currently unknown whether proteins could potentially be targeted by the inhibiting of protein synthesis. Under this circumstance, targeting protein translation could preferentially affect certain pathways, which could then be of therapeutic advantage when treating cancer. In this report, eukaryotic elongation factor-2 kinase (EEF2K), which is involved in protein translation, was shown to regulate cholesterol metabolism. Targeting EEF2K inhibited key parts of the cholesterol pathway in cancer cells, which could be rescued by the addition of exogenous cholesterol, suggesting that it is a potentially important pathway modulated by targeting this process. Specifically, targeting EEF2K significantly suppressed tumour cell growth by blocking mRNA translation of the cholesterol biosynthesis transcription factor, sterol regulatory element-binding protein (SREBP) 2, and the proteins it regulates. The process could be rescued by the addition of LDL cholesterol taken into the cells via non-receptor-mediated-uptake, which negated the need for SREBP2 protein. Thus, the levels of SREBP2 needed for cholesterol metabolism in cancer cells are therapeutically vulnerable by targeting protein translation. This is the first report to suggest that targeting EEF2K can be used to modulate cholesterol metabolism to treat cancer. MDPI 2022-03-23 /pmc/articles/PMC8998919/ /pubmed/35408842 http://dx.doi.org/10.3390/ijms23073481 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dinavahi, Saketh S. Chen, Yu-Chi Gowda, Raghavendra Dhanyamraju, Pavan Kumar Punnath, Kishore Desai, Dhimant Berg, Arthur Kimball, Scot R. Amin, Shantu Yang, Jin-Ming Robertson, Gavin P. Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title | Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title_full | Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title_fullStr | Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title_full_unstemmed | Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title_short | Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development |
title_sort | targeting protein translation in melanoma by inhibiting eef-2 kinase regulates cholesterol metabolism though srebp2 to inhibit tumour development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998919/ https://www.ncbi.nlm.nih.gov/pubmed/35408842 http://dx.doi.org/10.3390/ijms23073481 |
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