Methionine gamma lyase fused with S3 domain VGF forms octamers and adheres to tumor cells via binding to EGFR.

Autor: Bondarev NA; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Bagaeva DF; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Bazhenov SV; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Buben MM; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Bulushova NV; National Research Center Kurchatov Institute, Kurchatov Genomic Center, Moscow, 123182, Russia., Ryzhykau YL; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980, Dubna, Russia., Okhrimenko IS; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Zagryadskaya YA; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Maslov IV; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia., Anisimova NY; Department of Biochemistry, Patrice Lumumba People's Friendship University (RUDN University), Moscow, 117198, Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, 115478, Russia., Sokolova DV; Department of Biochemistry, Patrice Lumumba People's Friendship University (RUDN University), Moscow, 117198, Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, 115478, Russia; Center of Life Sciences, Sirius University of Science and Technology, Sochi, 354340, Russia., Kuklin AI; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980, Dubna, Russia., Pokrovsky VS; Department of Biochemistry, Patrice Lumumba People's Friendship University (RUDN University), Moscow, 117198, Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, 115478, Russia; Center of Life Sciences, Sirius University of Science and Technology, Sochi, 354340, Russia., Manukhov IV; Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia. Electronic address: manukhovi@mail.ru.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Jan 08; Vol. 691, pp. 149319. Date of Electronic Publication: 2023 Nov 25.
DOI: 10.1016/j.bbrc.2023.149319
Abstrakt: Methods for targeting enzymes exhibiting anticancer properties, such as methionine γ-lyase (MGL), have not yet been sufficiently developed. Here, we present the data describing the physico-chemical properties and cytotoxic effect of fusion protein MGL-S3 - MGL from Clostridium sporogenes translationally fused to S3 domain of the viral growth factor of smallpox. MGL-S3 has methioninase activity comparable to native MGL. In solution, MGL-S3 protein primarily forms octamers, whereas native MGL, on the contrary, usually forms tetramers. MGL-S3 binds to the surface of the neuroblastoma SH-SY5Y and epidermoid carcinoma A431 cells and, unlike native MGL, remains there and retains its cytotoxic effect after media removal. In HEK293T cells lacking EGFRs, no adhesion was recorded. Confocal fluorescence microscopy confirms the preferential adhesion of MGL-S3 to tumor cells, while it avoids getting into lysosomes. Both MGL and MGL-S3 arrest cell cycle of SH-SY5Y cells mainly in the G1 phase, while only MGL-S3 retains this ability after washing the cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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