Role of HSP90 in Cancer
HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal do...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Published: |
Multidisciplinary Digital Publishing Institute
2021
|
| Online Access: | https://hdl.handle.net/1721.1/133172 |
| _version_ | 1811089910949478400 |
|---|---|
| author | Birbo, Bereket Madu, Elechi E. Madu, Chikezie O. Jain, Aayush Lu, Yi |
| author_facet | Birbo, Bereket Madu, Elechi E. Madu, Chikezie O. Jain, Aayush Lu, Yi |
| author_sort | Birbo, Bereket |
| collection | MIT |
| description | HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90<i>α</i> and HSP90<i>β</i> are present in the cytoplasm; TRAP1 is present in the mitochondria; and GRP94 is present in the endoplasmic reticulum and is likely secreted due to post-translational modifications (PTM). HSP90 is also secreted into an extracellular environment via an exosome pathway that differs from the classic secretion pathway. Various co-chaperones are necessary for HSP90 to function. Elevated levels of HSP90 have been observed in patients with cancer. Despite this observation, the possible role of HSP90 in cancer was overlooked because the chaperone was also present in extreme amounts in normal cells and was vital to normal cell function, as observed when the drastic adverse effects resulting from gene knockout inhibited the production of this protein. Differences between normal HSP90 and HSP90 of the tumor phenotype have been better understood and have aided in making the chaperone protein a target for cancer drugs. One difference is in the conformation: HSP90 of the tumor phenotype is more susceptible to inhibitors. Since overexpression of HSP90 is a factor in tumorigenesis, HSP90 inhibitors have been studied to combat the adverse effects of HSP90 overexpression. Monotherapies using HSP90 inhibitors have shown some success; however, combination therapies have shown better results and are thus being studied for a more effective cancer treatment. |
| first_indexed | 2024-09-23T14:27:20Z |
| format | Article |
| id | mit-1721.1/133172 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:27:20Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1331722021-11-01T14:36:57Z Role of HSP90 in Cancer Birbo, Bereket Madu, Elechi E. Madu, Chikezie O. Jain, Aayush Lu, Yi HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90<i>α</i> and HSP90<i>β</i> are present in the cytoplasm; TRAP1 is present in the mitochondria; and GRP94 is present in the endoplasmic reticulum and is likely secreted due to post-translational modifications (PTM). HSP90 is also secreted into an extracellular environment via an exosome pathway that differs from the classic secretion pathway. Various co-chaperones are necessary for HSP90 to function. Elevated levels of HSP90 have been observed in patients with cancer. Despite this observation, the possible role of HSP90 in cancer was overlooked because the chaperone was also present in extreme amounts in normal cells and was vital to normal cell function, as observed when the drastic adverse effects resulting from gene knockout inhibited the production of this protein. Differences between normal HSP90 and HSP90 of the tumor phenotype have been better understood and have aided in making the chaperone protein a target for cancer drugs. One difference is in the conformation: HSP90 of the tumor phenotype is more susceptible to inhibitors. Since overexpression of HSP90 is a factor in tumorigenesis, HSP90 inhibitors have been studied to combat the adverse effects of HSP90 overexpression. Monotherapies using HSP90 inhibitors have shown some success; however, combination therapies have shown better results and are thus being studied for a more effective cancer treatment. 2021-10-27T17:13:59Z 2021-10-27T17:13:59Z 2021-09-25 2021-09-25T23:33:33Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133172 International Journal of Molecular Sciences 22 (19): 10317 (2021) PUBLISHER_CC http://dx.doi.org/10.3390/ijms221910317 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Birbo, Bereket Madu, Elechi E. Madu, Chikezie O. Jain, Aayush Lu, Yi Role of HSP90 in Cancer |
| title | Role of HSP90 in Cancer |
| title_full | Role of HSP90 in Cancer |
| title_fullStr | Role of HSP90 in Cancer |
| title_full_unstemmed | Role of HSP90 in Cancer |
| title_short | Role of HSP90 in Cancer |
| title_sort | role of hsp90 in cancer |
| url | https://hdl.handle.net/1721.1/133172 |
| work_keys_str_mv | AT birbobereket roleofhsp90incancer AT maduelechie roleofhsp90incancer AT maduchikezieo roleofhsp90incancer AT jainaayush roleofhsp90incancer AT luyi roleofhsp90incancer |