HSPBP1 in complex with the peptide of the innate immunity protein TAG7 is able to lyse tumor cells carrying TNFR1 receptor

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The search for new cytotoxic agents capable of lysing tumor cells is an important task in the fight against cancer. Here we have shown that the protein HspBP1, the chaperone of the heat shock protein Hsp70, is able to form a complex with the previously discovered peptide (17.1) of the innate immunity protein Tag7. Experiments using thermophoresis have demonstrated that the affinity of the Tag7 protein peptide 17.1 to the HspBP1 molecule is 100 times higher than that of the full-sized Tag7 molecule. The addition of the 17.1-HspBP1 complex to tumor cells induces apoptosis and necroptosis in them. The results obtained in this work can be used to develop promising antitumor drugs.

Full Text

Restricted Access

About the authors

E. A. Romanova

Institute of Gene Biology of the Russian Academy of Sciences

Email: yashin_co@mail.ru
Russian Federation, Moscow

D. M. Yurkina

Institute of Gene Biology of the Russian Academy of Sciences

Email: yashin_co@mail.ru
Russian Federation, Moscow

D. V. Yashin

Institute of Gene Biology of the Russian Academy of Sciences

Author for correspondence.
Email: yashin_co@mail.ru
Russian Federation, Moscow

L. P. Sashchenko

Institute of Gene Biology of the Russian Academy of Sciences

Email: yashin_co@mail.ru
Russian Federation, Moscow

G. P. Georgiev

Institute of Gene Biology of the Russian Academy of Sciences

Email: yashin_co@mail.ru

Academician of the RAS

Russian Federation, Moscow

References

  1. Carswell E. A., et al. An endotoxin-induced serum factor that causes necrosis of tumors // Proc. Natl. Acad. Sci. USA. 1975. V. 72. P. 3666–3670.
  2. Siegmund D., Wajant H. TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond // Nat. Rev. Rheumatol. 2023. V. 19. P. 576–591.
  3. Huyghe J., Priem D., Bertrand M. J.M. Cell death checkpoints in the TNF pathway // Trends Immunol. 2023. V. 44. P. 628–643.
  4. Shi G., Hu Y. TNFR1 and TNFR2, Which Link NF-κB Activation, Drive Lung Cancer Progression, Cell Dedifferentiation, and Metastasis // Cancers (Basel). 2023. V. 15. P. 4299.
  5. Gough P., Myles I. A. Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects // Front Immunol. 2020. V. 11. P. 585880.
  6. Ashkenazi A., Salvesen G. Regulated cell death: signaling and mechanisms // Annu Rev Cell Dev. Biol. 2014. V. 30. P. 337–356.
  7. Roberts J. Z., Crawford N., Longley D. B. The role of Ubiquitination in Apoptosis and Necroptosis // Cell Death Differ. 2022. V. 29. P. 272–284.
  8. Kustikova O. S., et al. Cloning of the tag7 gene expressed in metastatic mouse tumors // Genetika. 1996. V. 32. P. 621–628.
  9. Yashin D. V., et al. Tag7 (PGLYRP1) in Complex with Hsp70 Induces Alternative Cytotoxic Processes in Tumor Cells via TNFR1 Receptor // J Biol. Chem. 2015. V. 290. P. 21724–21731.
  10. Yashin D. V., et al. The Tag7-Hsp70 cytotoxic complex induces tumor cell necroptosis via permeabilisation of lysosomes and mitochondria // Biochimie. 2016. V. 123. P. 32–36.
  11. Yashin D. V., et al. The heat shock-binding protein (HspBP1) protects cells against the cytotoxic action of the Tag7-Hsp70 complex // J Biol. Chem. 2011. V. 286. P. 10258–10264.
  12. Bracher A., Verghese J, Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Proteins // Subcell Biochem. 2023. V. 101. P. 1–39.
  13. Yurkina D. M., et al. Short Peptides of Innate Immunity Protein Tag7 (PGLYRP1) Selectively Induce Inhibition or Activation of Tumor Cell Death via TNF Receptor // Int J Mol Sci. 2023. V. 24. P. 11363.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. (a) The addition of an increasing concentration of HspBP1 to the Tag7-Hsp70 complex inhibits its cytotoxic activity. (b) The addition of an increasing concentration of Hsp70 to the Tag7-HspBP1 complex leads to the appearance of cytotoxic activity.

Download (194KB)
Indexing metadata
3. Fig. 2. Application of HspBP1 to 17.1-Sepharose (experiment) or to pure Sepharose (control), resolved using 12% SDS-PAAG and manifested by antibodies to HspBP1.

Download (76KB)
Indexing metadata
4. Fig. 3. Thermophoretic dissociation curves in the interaction of Tag7-HspBP1 (a) and 17.1-HspBP1 (b)

Download (268KB)
Indexing metadata
5. Fig. 4. Cytotoxic activity of complexes after 3 (a) and 20 hours (b) incubation with L929 tumor cells. * – p < 0.05

Download (298KB)
Indexing metadata

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies