With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage
Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triag...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/3121 |
| _version_ | 1797510811720089600 |
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| author | Selin Altinok Rebekah Sanchez-Hodge Mariah Stewart Kaitlan Smith Jonathan C. Schisler |
| author_facet | Selin Altinok Rebekah Sanchez-Hodge Mariah Stewart Kaitlan Smith Jonathan C. Schisler |
| author_sort | Selin Altinok |
| collection | DOAJ |
| description | Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones. |
| first_indexed | 2024-03-10T05:36:34Z |
| format | Article |
| id | doaj.art-a45b39cdebdc4eadbbfe89c4641cfb01 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:36:34Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a45b39cdebdc4eadbbfe89c4641cfb012023-11-22T22:51:36ZengMDPI AGCells2073-44092021-11-011011312110.3390/cells10113121With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein TriageSelin Altinok0Rebekah Sanchez-Hodge1Mariah Stewart2Kaitlan Smith3Jonathan C. Schisler4Computational Medicine Program, Department of Pharmacology, Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAComputational Medicine Program, Department of Pharmacology, Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAComputational Medicine Program, Department of Pharmacology, Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAComputational Medicine Program, Department of Pharmacology, Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAComputational Medicine Program, Department of Pharmacology, Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAHeat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.https://www.mdpi.com/2073-4409/10/11/3121heat shock proteinsco-chaperonesprotein quality controlprotein foldingprotein degradationcardioprotection |
| spellingShingle | Selin Altinok Rebekah Sanchez-Hodge Mariah Stewart Kaitlan Smith Jonathan C. Schisler With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage Cells heat shock proteins co-chaperones protein quality control protein folding protein degradation cardioprotection |
| title | With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage |
| title_full | With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage |
| title_fullStr | With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage |
| title_full_unstemmed | With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage |
| title_short | With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage |
| title_sort | with or without you co chaperones mediate health and disease by modifying chaperone function and protein triage |
| topic | heat shock proteins co-chaperones protein quality control protein folding protein degradation cardioprotection |
| url | https://www.mdpi.com/2073-4409/10/11/3121 |
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