Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery
Modulation of protein fate decision and protein homeostasis plays a significant role in altering the protein level, which acts as an orientation to develop drugs with new mechanisms. The molecular chaperones exert significant biological functions on modulation of protein fate decision and protein ho...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-10-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383519315266 |
| _version_ | 1828786712391712768 |
|---|---|
| author | Lei Wang Xiaoli Xu Zhengyu Jiang Qidong You |
| author_facet | Lei Wang Xiaoli Xu Zhengyu Jiang Qidong You |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | Modulation of protein fate decision and protein homeostasis plays a significant role in altering the protein level, which acts as an orientation to develop drugs with new mechanisms. The molecular chaperones exert significant biological functions on modulation of protein fate decision and protein homeostasis under constantly changing environmental conditions through extensive protein–protein interactions (PPIs) with their client proteins. With the help of molecular chaperone machinery, the processes of protein folding, trafficking, quality control and degradation of client proteins could be arranged properly. The core members of molecular chaperones, including heat shock proteins (HSPs) family and their co-chaperones, are emerging as potential drug targets since they are involved in numerous disease conditions. Development of small molecule modulators targeting not only chaperones themselves but also the PPIs among chaperones, co-chaperones and clients is attracting more and more attention. These modulators are widely used as chemical tools to study chaperone networks as well as potential drug candidates for a broader set of diseases. Here, we reviewed the key checkpoints of molecular chaperone machinery HSPs as well as their co-chaperones to discuss the small molecules targeting on them for modulation of protein fate decision. |
| first_indexed | 2024-12-12T00:17:40Z |
| format | Article |
| id | doaj.art-99090f989082460e96bc4e6ee5ddbd6e |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-12T00:17:40Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-99090f989082460e96bc4e6ee5ddbd6e2022-12-22T00:44:50ZengElsevierActa Pharmaceutica Sinica B2211-38352020-10-01101019041925Modulation of protein fate decision by small molecules: targeting molecular chaperone machineryLei Wang0Xiaoli Xu1Zhengyu Jiang2Qidong You3State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors. Tel./fax: +86 25 83271351.State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors. Tel./fax: +86 25 83271351.Modulation of protein fate decision and protein homeostasis plays a significant role in altering the protein level, which acts as an orientation to develop drugs with new mechanisms. The molecular chaperones exert significant biological functions on modulation of protein fate decision and protein homeostasis under constantly changing environmental conditions through extensive protein–protein interactions (PPIs) with their client proteins. With the help of molecular chaperone machinery, the processes of protein folding, trafficking, quality control and degradation of client proteins could be arranged properly. The core members of molecular chaperones, including heat shock proteins (HSPs) family and their co-chaperones, are emerging as potential drug targets since they are involved in numerous disease conditions. Development of small molecule modulators targeting not only chaperones themselves but also the PPIs among chaperones, co-chaperones and clients is attracting more and more attention. These modulators are widely used as chemical tools to study chaperone networks as well as potential drug candidates for a broader set of diseases. Here, we reviewed the key checkpoints of molecular chaperone machinery HSPs as well as their co-chaperones to discuss the small molecules targeting on them for modulation of protein fate decision.http://www.sciencedirect.com/science/article/pii/S2211383519315266Molecular chaperoneHeat shock protein familySmall molecule inhibitorsProtein fateProtein–protein interaction |
| spellingShingle | Lei Wang Xiaoli Xu Zhengyu Jiang Qidong You Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery Acta Pharmaceutica Sinica B Molecular chaperone Heat shock protein family Small molecule inhibitors Protein fate Protein–protein interaction |
| title | Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery |
| title_full | Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery |
| title_fullStr | Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery |
| title_full_unstemmed | Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery |
| title_short | Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery |
| title_sort | modulation of protein fate decision by small molecules targeting molecular chaperone machinery |
| topic | Molecular chaperone Heat shock protein family Small molecule inhibitors Protein fate Protein–protein interaction |
| url | http://www.sciencedirect.com/science/article/pii/S2211383519315266 |
| work_keys_str_mv | AT leiwang modulationofproteinfatedecisionbysmallmoleculestargetingmolecularchaperonemachinery AT xiaolixu modulationofproteinfatedecisionbysmallmoleculestargetingmolecularchaperonemachinery AT zhengyujiang modulationofproteinfatedecisionbysmallmoleculestargetingmolecularchaperonemachinery AT qidongyou modulationofproteinfatedecisionbysmallmoleculestargetingmolecularchaperonemachinery |