Singh Manish Kumar, Han Sunhee, Ju Songhyun, Ranbhise Jyotsna S, Ha Joohun, Yeo Seung Geun, Kim Sung Soo, Kang Insug
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
Cells. 2025 Mar 29;14(7):509. doi: 10.3390/cells14070509.
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.
热休克蛋白70（Hsp70）是一种70千道尔顿的分子伴侣，在维持蛋白质稳态中起着关键作用。它与共伴侣蛋白的DnaJ家族相互作用，以调节参与各种细胞过程的客户蛋白的功能，包括跨膜运输、细胞外囊泡运输、复合物形成和蛋白酶体降解。它存在于多个细胞器中，使其能够介导应激反应、细胞凋亡和炎症，突出了其在疾病进展中的重要性。最初因其在蛋白质折叠、解聚和降解中的重要作用而被认识，后来的研究表明它与多种人类疾病有关。值得注意的是，Hsp70在多种癌症中上调，在这些癌症中它促进肿瘤增殖并作为肿瘤免疫原。此外，表观伴侣组网络稳定大型和长寿组装体中的蛋白质-蛋白质相互作用，促进癌症进展和神经退行性变。然而，肿瘤微环境中的细胞外Hsp70（eHsp70）可以激活免疫细胞，如自然杀伤（NK）细胞，表明其在免疫治疗干预（包括嵌合抗原受体T细胞疗法）中的潜力。鉴于其在细胞生理学和病理学中的多方面作用，Hsp70作为多种人类疾病的生物标志物和治疗靶点具有巨大潜力。本综述强调了Hsp70的结构和功能重要性，探讨了其在疾病发病机制中的作用，并讨论了其在诊断和治疗应用中的潜力。
