Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders
The Hsp90 molecular chaperone, along with a set of approximately 50 cochaperones, mediates the folding and activation of hundreds of cellular proteins in an ATP-dependent cycle. Cochaperones differ in how they interact with Hsp90 and their ability to modulate ATPase activity of Hsp90. Cochaperones o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.787260/full |
| _version_ | 1818722712731779072 |
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| author | Jill L. Johnson |
| author_facet | Jill L. Johnson |
| author_sort | Jill L. Johnson |
| collection | DOAJ |
| description | The Hsp90 molecular chaperone, along with a set of approximately 50 cochaperones, mediates the folding and activation of hundreds of cellular proteins in an ATP-dependent cycle. Cochaperones differ in how they interact with Hsp90 and their ability to modulate ATPase activity of Hsp90. Cochaperones often compete for the same binding site on Hsp90, and changes in levels of cochaperone expression that occur during neurodegeneration, cancer, or aging may result in altered Hsp90-cochaperone complexes and client activity. This review summarizes information about loss-of-function mutations of individual cochaperones and discusses the overall association of cochaperone alterations with a broad range of diseases. Cochaperone mutations result in ciliary or muscle defects, neurological development or degeneration disorders, and other disorders. In many cases, diseases were linked to defects in established cochaperone-client interactions. A better understanding of the functional consequences of defective cochaperones will provide new insights into their functions and may lead to specialized approaches to modulate Hsp90 functions and treat some of these human disorders. |
| first_indexed | 2024-12-17T20:58:59Z |
| format | Article |
| id | doaj.art-22f5be2df1a74a61a1a9e261c331623d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-17T20:58:59Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-22f5be2df1a74a61a1a9e261c331623d2022-12-21T21:32:46ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-12-01810.3389/fmolb.2021.787260787260Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human DisordersJill L. JohnsonThe Hsp90 molecular chaperone, along with a set of approximately 50 cochaperones, mediates the folding and activation of hundreds of cellular proteins in an ATP-dependent cycle. Cochaperones differ in how they interact with Hsp90 and their ability to modulate ATPase activity of Hsp90. Cochaperones often compete for the same binding site on Hsp90, and changes in levels of cochaperone expression that occur during neurodegeneration, cancer, or aging may result in altered Hsp90-cochaperone complexes and client activity. This review summarizes information about loss-of-function mutations of individual cochaperones and discusses the overall association of cochaperone alterations with a broad range of diseases. Cochaperone mutations result in ciliary or muscle defects, neurological development or degeneration disorders, and other disorders. In many cases, diseases were linked to defects in established cochaperone-client interactions. A better understanding of the functional consequences of defective cochaperones will provide new insights into their functions and may lead to specialized approaches to modulate Hsp90 functions and treat some of these human disorders.https://www.frontiersin.org/articles/10.3389/fmolb.2021.787260/fullCS domainAha1tetratricopeptide repeatFKBPFNIP1chaperonopathy |
| spellingShingle | Jill L. Johnson Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders Frontiers in Molecular Biosciences CS domain Aha1 tetratricopeptide repeat FKBP FNIP1 chaperonopathy |
| title | Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders |
| title_full | Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders |
| title_fullStr | Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders |
| title_full_unstemmed | Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders |
| title_short | Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders |
| title_sort | mutations in hsp90 cochaperones result in a wide variety of human disorders |
| topic | CS domain Aha1 tetratricopeptide repeat FKBP FNIP1 chaperonopathy |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.787260/full |
| work_keys_str_mv | AT jillljohnson mutationsinhsp90cochaperonesresultinawidevarietyofhumandisorders |