Bcl-B: an “unknown” protein of the Bcl-2 family

Pervushin, N. V.; Kopeina, G. S.; Zhivotovsky, B.

doi:10.1186/s13062-023-00431-4

Cited by 2 publications

(1 citation statement)

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“…It is known that the TNFR1 receptor induces alternative processes of the program of the cell’s death: apoptosis and necroptosis [ 30 , 31 , 32 ]. Previously, we showed that necroptosis induced by the Tag7-Hsp70 complex is carried out with the participation of lysosomes and mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Mts1 (S100A4) and Its Peptide Demonstrate Cytotoxic Activity in Complex with Tag7 (PGLYRP1) Peptide

Yurkina,

Romanova,

Shcherbakov

et al. 2024

IJMS

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Receptors of cytokines are major regulators of the immune response. In this work, we have discovered two new ligands that can activate the TNFR1 (tumor necrosis factor receptor 1) receptor. Earlier, we found that the peptide of the Tag (PGLYRP1) protein designated 17.1 can interact with the TNFR1 receptor. Here, we have found that the Mts1 (S100A4) protein interacts with this peptide with a high affinity (Kd = 1.28 × 10−8 M), and that this complex is cytotoxic to cancer cells that have the TNFR1 receptor on their surface. This complex induces both apoptosis and necroptosis in cancer cells with the involvement of mitochondria and lysosomes in cell death signal transduction. Moreover, we have succeeded in locating the Mts1 fragment that is responsible for protein–peptide interaction, which highly specifically interacts with the Tag7 protein (Kd = 2.96 nM). The isolated Mts1 peptide M7 also forms a complex with 17.1, and this peptide–peptide complex also induces the TNFR1 receptor-dependent cell death. Molecular docking and molecular dynamics experiments show the amino acids involved in peptide binding and that may be used for peptidomimetics’ development. Thus, two new cytotoxic complexes were created that were able to induce the death of tumor cells via the TNFR1 receptor. These results may be used in therapy for both cancer and autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%