TRAP1 Chaperones the Metabolic Switch in Cancer
Mitochondrial function is dependent on molecular chaperones, primarily due to their necessity in the formation of respiratory complexes and clearance of misfolded proteins. Heat shock proteins (Hsps) are a subset of molecular chaperones that function in all subcellular compartments, both constitutiv...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/6/786 |
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| author | Laura A. Wengert Sarah J. Backe Dimitra Bourboulia Mehdi Mollapour Mark R. Woodford |
| author_facet | Laura A. Wengert Sarah J. Backe Dimitra Bourboulia Mehdi Mollapour Mark R. Woodford |
| author_sort | Laura A. Wengert |
| collection | DOAJ |
| description | Mitochondrial function is dependent on molecular chaperones, primarily due to their necessity in the formation of respiratory complexes and clearance of misfolded proteins. Heat shock proteins (Hsps) are a subset of molecular chaperones that function in all subcellular compartments, both constitutively and in response to stress. The Hsp90 chaperone TNF-receptor-associated protein-1 (TRAP1) is primarily localized to the mitochondria and controls both cellular metabolic reprogramming and mitochondrial apoptosis. TRAP1 upregulation facilitates the growth and progression of many cancers by promoting glycolytic metabolism and antagonizing the mitochondrial permeability transition that precedes multiple cell death pathways. TRAP1 attenuation induces apoptosis in cellular models of cancer, identifying TRAP1 as a potential therapeutic target in cancer. Similar to cytosolic Hsp90 proteins, TRAP1 is also subject to post-translational modifications (PTM) that regulate its function and mediate its impact on downstream effectors, or ‘clients’. However, few effectors have been identified to date. Here, we will discuss the consequence of TRAP1 deregulation in cancer and the impact of post-translational modification on the known functions of TRAP1. |
| first_indexed | 2024-03-10T00:18:53Z |
| format | Article |
| id | doaj.art-5d47277248ea418dae3ad6a40be19fdb |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:18:53Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5d47277248ea418dae3ad6a40be19fdb2023-11-23T15:46:54ZengMDPI AGBiomolecules2218-273X2022-06-0112678610.3390/biom12060786TRAP1 Chaperones the Metabolic Switch in CancerLaura A. Wengert0Sarah J. Backe1Dimitra Bourboulia2Mehdi Mollapour3Mark R. Woodford4Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USADepartment of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USADepartment of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USADepartment of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USADepartment of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USAMitochondrial function is dependent on molecular chaperones, primarily due to their necessity in the formation of respiratory complexes and clearance of misfolded proteins. Heat shock proteins (Hsps) are a subset of molecular chaperones that function in all subcellular compartments, both constitutively and in response to stress. The Hsp90 chaperone TNF-receptor-associated protein-1 (TRAP1) is primarily localized to the mitochondria and controls both cellular metabolic reprogramming and mitochondrial apoptosis. TRAP1 upregulation facilitates the growth and progression of many cancers by promoting glycolytic metabolism and antagonizing the mitochondrial permeability transition that precedes multiple cell death pathways. TRAP1 attenuation induces apoptosis in cellular models of cancer, identifying TRAP1 as a potential therapeutic target in cancer. Similar to cytosolic Hsp90 proteins, TRAP1 is also subject to post-translational modifications (PTM) that regulate its function and mediate its impact on downstream effectors, or ‘clients’. However, few effectors have been identified to date. Here, we will discuss the consequence of TRAP1 deregulation in cancer and the impact of post-translational modification on the known functions of TRAP1.https://www.mdpi.com/2218-273X/12/6/786TRAP1Hsp90chaperonepost-translational modificationcancermitochondria |
| spellingShingle | Laura A. Wengert Sarah J. Backe Dimitra Bourboulia Mehdi Mollapour Mark R. Woodford TRAP1 Chaperones the Metabolic Switch in Cancer Biomolecules TRAP1 Hsp90 chaperone post-translational modification cancer mitochondria |
| title | TRAP1 Chaperones the Metabolic Switch in Cancer |
| title_full | TRAP1 Chaperones the Metabolic Switch in Cancer |
| title_fullStr | TRAP1 Chaperones the Metabolic Switch in Cancer |
| title_full_unstemmed | TRAP1 Chaperones the Metabolic Switch in Cancer |
| title_short | TRAP1 Chaperones the Metabolic Switch in Cancer |
| title_sort | trap1 chaperones the metabolic switch in cancer |
| topic | TRAP1 Hsp90 chaperone post-translational modification cancer mitochondria |
| url | https://www.mdpi.com/2218-273X/12/6/786 |
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