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

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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.

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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

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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.

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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.

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

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

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