MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1
The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, pr...
| Main Authors: | , , , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
eLife Sciences Publications Ltd
2021-01-01
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| Colecção: | eLife |
| Assuntos: | |
| Acesso em linha: | https://elifesciences.org/articles/60191 |
| _version_ | 1829097316493033472 |
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| author | Tessa M Popay Jing Wang Clare M Adams Gregory Caleb Howard Simona G Codreanu Stacy D Sherrod John A McLean Lance R Thomas Shelly L Lorey Yuichi J Machida April M Weissmiller Christine M Eischen Qi Liu William P Tansey |
| author_facet | Tessa M Popay Jing Wang Clare M Adams Gregory Caleb Howard Simona G Codreanu Stacy D Sherrod John A McLean Lance R Thomas Shelly L Lorey Yuichi J Machida April M Weissmiller Christine M Eischen Qi Liu William P Tansey |
| author_sort | Tessa M Popay |
| collection | DOAJ |
| description | The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)–1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies. |
| first_indexed | 2024-04-11T09:11:56Z |
| format | Article |
| id | doaj.art-858ae447047d4222bb272f96fbb33a0c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:11:56Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-858ae447047d4222bb272f96fbb33a0c2022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.60191MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1Tessa M Popay0https://orcid.org/0000-0002-4694-8804Jing Wang1Clare M Adams2Gregory Caleb Howard3Simona G Codreanu4Stacy D Sherrod5https://orcid.org/0000-0002-2346-230XJohn A McLean6Lance R Thomas7Shelly L Lorey8Yuichi J Machida9April M Weissmiller10Christine M Eischen11https://orcid.org/0000-0003-4618-8996Qi Liu12William P Tansey13https://orcid.org/0000-0002-3900-0978Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, United States; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United StatesCenter for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United StatesCenter for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United StatesCenter for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Oncology, Mayo Clinic, Rochester, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, United StatesDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, United States; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, United StatesThe oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)–1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.https://elifesciences.org/articles/60191cancerMYCribosome biogenesis |
| spellingShingle | Tessa M Popay Jing Wang Clare M Adams Gregory Caleb Howard Simona G Codreanu Stacy D Sherrod John A McLean Lance R Thomas Shelly L Lorey Yuichi J Machida April M Weissmiller Christine M Eischen Qi Liu William P Tansey MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 eLife cancer MYC ribosome biogenesis |
| title | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 |
| title_full | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 |
| title_fullStr | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 |
| title_full_unstemmed | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 |
| title_short | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1 |
| title_sort | myc regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor 1 |
| topic | cancer MYC ribosome biogenesis |
| url | https://elifesciences.org/articles/60191 |
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