Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease
Hsp70, a 70 kDa molecular chaperone, plays a crucial role in maintaining protein homeostasis. It interacts with the DnaJ family of co-chaperones to modulate the functions of client proteins involved in various cellular processes, including transmembrane transport, extracellular vesicle trafficking,...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/7/509 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730754252111872 |
|---|---|
| author | Manish Kumar Singh Sunhee Han Songhyun Ju Jyotsna S. Ranbhise Joohun Ha Seung Geun Yeo Sung Soo Kim Insug Kang |
| author_facet | Manish Kumar Singh Sunhee Han Songhyun Ju Jyotsna S. Ranbhise Joohun Ha Seung Geun Yeo Sung Soo Kim Insug Kang |
| author_sort | Manish Kumar Singh |
| collection | DOAJ |
| description | Hsp70, a 70 kDa molecular chaperone, plays a crucial role in maintaining protein homeostasis. It interacts with the DnaJ family of co-chaperones to modulate the functions of client proteins involved in various cellular processes, including transmembrane transport, extracellular vesicle trafficking, complex formation, and proteasomal degradation. Its presence in multiple cellular organelles enables it to mediate stress responses, apoptosis, and inflammation, highlighting its significance in disease progression. Initially recognized for its essential roles in protein folding, disaggregation, and degradation, later studies have demonstrated its involvement in several human diseases. Notably, Hsp70 is upregulated in multiple cancers, where it promotes tumor proliferation and serves as a tumor immunogen. Additionally, epichaperome networks stabilize protein–protein interactions in large and long-lived assemblies, contributing to both cancer progression and neurodegeneration. However, extracellular Hsp70 (eHsp70) in the tumor microenvironment can activate immune cells, such as natural killer (NK) cells, suggesting its potential in immunotherapeutic interventions, including CAR T-cell therapy. Given its multifaceted roles in cellular physiology and pathology, Hsp70 holds immense potential as both a biomarker and a therapeutic target across multiple human diseases. This review highlights the structural and functional importance of Hsp70, explores its role in disease pathogenesis, and discusses its potential in diagnostic and therapeutic applications. |
| format | Article |
| id | doaj-art-e132e69a2e4f44b0895117784b4f7523 |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-e132e69a2e4f44b0895117784b4f75232025-08-20T03:08:46ZengMDPI AGCells2073-44092025-03-0114750910.3390/cells14070509Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human DiseaseManish Kumar Singh0Sunhee Han1Songhyun Ju2Jyotsna S. Ranbhise3Joohun Ha4Seung Geun Yeo5Sung Soo Kim6Insug Kang7Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Otorhinolaryngology—Head and Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaHsp70, a 70 kDa molecular chaperone, plays a crucial role in maintaining protein homeostasis. It interacts with the DnaJ family of co-chaperones to modulate the functions of client proteins involved in various cellular processes, including transmembrane transport, extracellular vesicle trafficking, complex formation, and proteasomal degradation. Its presence in multiple cellular organelles enables it to mediate stress responses, apoptosis, and inflammation, highlighting its significance in disease progression. Initially recognized for its essential roles in protein folding, disaggregation, and degradation, later studies have demonstrated its involvement in several human diseases. Notably, Hsp70 is upregulated in multiple cancers, where it promotes tumor proliferation and serves as a tumor immunogen. Additionally, epichaperome networks stabilize protein–protein interactions in large and long-lived assemblies, contributing to both cancer progression and neurodegeneration. However, extracellular Hsp70 (eHsp70) in the tumor microenvironment can activate immune cells, such as natural killer (NK) cells, suggesting its potential in immunotherapeutic interventions, including CAR T-cell therapy. Given its multifaceted roles in cellular physiology and pathology, Hsp70 holds immense potential as both a biomarker and a therapeutic target across multiple human diseases. This review highlights the structural and functional importance of Hsp70, explores its role in disease pathogenesis, and discusses its potential in diagnostic and therapeutic applications.https://www.mdpi.com/2073-4409/14/7/509cancerepichaperomeHsp70inflammationapoptosisprotein-folding |
| spellingShingle | Manish Kumar Singh Sunhee Han Songhyun Ju Jyotsna S. Ranbhise Joohun Ha Seung Geun Yeo Sung Soo Kim Insug Kang Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease Cells cancer epichaperome Hsp70 inflammation apoptosis protein-folding |
| title | Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease |
| title_full | Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease |
| title_fullStr | Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease |
| title_full_unstemmed | Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease |
| title_short | Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease |
| title_sort | hsp70 a multifunctional chaperone in maintaining proteostasis and its implications in human disease |
| topic | cancer epichaperome Hsp70 inflammation apoptosis protein-folding |
| url | https://www.mdpi.com/2073-4409/14/7/509 |
| work_keys_str_mv | AT manishkumarsingh hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT sunheehan hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT songhyunju hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT jyotsnasranbhise hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT joohunha hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT seunggeunyeo hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT sungsookim hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease AT insugkang hsp70amultifunctionalchaperoneinmaintainingproteostasisanditsimplicationsinhumandisease |