Advances in the structures, mechanisms and targeting of molecular chaperones

Hartl, F. U. & Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 16, 574–581 (2009).

Article  CAS  PubMed  Google Scholar 

Hartl, F. U. Molecular chaperones in cellular protein folding. Nature 381, 571–579 (1996).

Article  CAS  PubMed  Google Scholar 

Frydman, J. Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu. Rev. Biochem. 70, 603–647 (2001).

Article  CAS  PubMed  Google Scholar 

Wu, J. et al. Heat shock proteins and cancer. Trends Pharm. Sci. 38, 226–256 (2017).

Article  CAS  PubMed  Google Scholar 

Lubkowska, A., Pluta, W., Strońska, A. & Lalko, A. Role of heat shock proteins (HSP70 and HSP90) in viral infection. Int. J. Mol. Sci. 22, 9366 (2021).

Ashburner, M. & Bonner, J. J. The induction of gene activity in drosophilia by heat shock. Cell 17, 241–254 (1979).

Article  CAS  PubMed  Google Scholar 

Kampinga, H. H. et al. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14, 105–111 (2009).

Article  CAS  PubMed  Google Scholar 

Mirikar, D., Bushman, Y. & Truman, A. W. Structural transitions modulate the chaperone activities of Grp94. Trends Biochem. Sci. 49, 752–753 (2024).

Article  CAS  PubMed  Google Scholar 

Dharaskar, S. P., Paithankar, K. & Amere Subbarao, S. Analysis and functional relevance of the chaperone TRAP-1 interactome in the metabolic regulation and mitochondrial integrity of cancer cells. Sci. Rep. 13, 7584 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lees-Miller, S. P. & Anderson, C. W. Two human 90-kDa heat shock proteins are phosphorylated in vivo at conserved serines that are phosphorylated in vitro by casein kinase II. J. Biol. Chem. 264, 2431–2437 (1989).

Article  CAS  PubMed  Google Scholar 

Velasco-Carneros, L. et al. Pseudophosphorylation of single residues of the J domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system. Protein Sci. 33, e5105 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kandasamy, G. & Andréasson, C. Hsp70-Hsp110 chaperones deliver ubiquitin-dependent and -independent substrates to the 26S proteasome for proteolysis in yeast. J. Cell Sci. 131, jcs210948 (2018).

Article  PubMed  Google Scholar 

Havalová, H. et al. Mitochondrial HSP70 chaperone system—the influence of post-translational modifications and involvement in human diseases. Int. J. Mol. Sci. 22, 8077 (2021).

Piva, F., Cecati, M. & Giulietti, M. Gaining new insights on the Hsp90 regulatory network. Bioinformation 16, 17–20 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Hu, C. et al. Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities. MedComm 3, e161 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Singh, M. K. et al. Heat Shock response and heat shock proteins: current understanding and future opportunities in human diseases. Int. J. Mol. Sci. 25, 4209 (2024).

Tukaj, S. & Sitko, K. Heat shock protein 90 (Hsp90) and Hsp70 as potential therapeutic targets in autoimmune skin diseases. Biomolecules 12, 1153 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wei, H. et al. Heat shock protein 90: biological functions, diseases, and therapeutic targets. MedComm 5, e470 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Min, L. et al. Targeting HSP90 in gynecologic cancer: molecular mechanisms and therapeutic approaches. Cell Biochem. Biophys. https://doi.org/10.1007/s12013-024-01502-7 (2024).

Rong, B. & Yang, S. Molecular mechanism and targeted therapy of Hsp90 involved in lung cancer: new discoveries and developments (Review). Int. J. Oncol. 52, 321–336 (2018).

CAS  PubMed  Google Scholar 

Qin, L. et al. Biological characteristics of heat shock protein 90 in human liver cancer cells. Am. J. Transl. Res 11, 2477–2483 (2019).

CAS  PubMed  PubMed Central  Google Scholar 

Wang, X. et al. The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proc. Natl. Acad. Sci. USA 106, 21288–21293 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sun, H. et al. The protein-protein interaction network and clinical significance of heat-shock proteins in esophageal squamous cell carcinoma. Amino Acids 50, 685–697 (2018).

Article  CAS  PubMed  Google Scholar 

Nakhjavani, M. et al. Increased serum HSP70 levels are associated with the duration of diabetes. Cell Stress Chaperones 15, 959–964 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Waza, M. et al. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med. 11, 1088–1095 (2005).

Article  CAS  PubMed  Google Scholar 

Wang, L., Xu, X., Jiang, Z. & You, Q. Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery. Acta Pharm. Sin. B 10, 1904–1925 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Livak, K. J. et al. Sequence organization and transcription at two heat shock loci in Drosophila. Proc. Natl. Acad. Sci. USA 75, 5613–5617 (1978).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schedl, P. et al. Two hybrid plasmids with D. melanogaster DNA sequences complementary to mRNA coding for the major heat shock protein. Cell 14, 921–929 (1978).

Article  CAS  PubMed  Google Scholar 

Ritossa, F. A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia 18, 571–573 (1962).

Article  CAS  Google Scholar 

Sondermeijer, P. J. & Lubsen, N. H. Heat-shock peptides in Drosophila hydei and their synthesis in vitro. Eur. J. Biochem. 88, 331–339 (1978).

Article  CAS  PubMed  Google Scholar 

Moran, L. et al. Heat shock of Drosophila melanogaster induces the synthesis of new messenger RNAs and proteins. Philos. Trans. R. Soc. Lond. B Biol. Sci. 283, 391–406 (1978).

Article  CAS  PubMed  Google Scholar 

Qian, Y. Q., Patel, D., Hartl, F. U. & McColl, D. J. Nuclear magnetic resonance solution structure of the human Hsp40 (HDJ-1) J domain. J. Mol. Biol. 260, 224–235 (1996).

Article  CAS  PubMed  Google Scholar 

O’Brien, M. C. & McKay, D. B. Threonine 204 of the chaperone protein Hsc70 influences the structure of the active site, but is not essential for ATP hydrolysis. J. Biol. Chem. 268, 24323–24329 (1993).

Article  PubMed  Google Scholar 

Soldano, K. L., Jivan, A., Nicchitta, C. V. & Gewirth, D. T. Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulation. J. Biol. Chem. 278, 48330–48338 (2003).

Article  CAS  PubMed  Google Scholar 

Lavery, L. A. et al. Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism. Mol. Cell 53, 330–343 (2014).

Article 

Comments (0)

No login
gif