Short Peptides of Innate Immunity Protein Tag7 (PGLYRP1) Selectively Induce Inhibition or Activation of Tumor Cell Death via TNF Receptor

Yurkina, Daria M.; Sharapova, Tatiana N.; Romanova, Elena A.; Yashin, Denis V.; Sashchenko, Lidia P.

doi:10.3390/ijms241411363

Cited by 4 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, using limited trypsinolysis, we identified the peptide 17.1-protein Tag7, which causes the bifunctional activity of this TNFR1 ligand: inhibition of the cytotoxic action of TNF or induction of cytotoxic activity using the Hsp70 coactivator. Shortened fragments of this peptide were also identified, responsible for only one function: inhibitory or cytotoxic [34]. Inhibitory peptides had a noticeable protective effect on the development of CFA-dependent autoimmune arthritis [40].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have identified peptide fragments of the TNFR1 ligand, the Tag7 protein, which performs only one function: either the inhibition of the TNF interaction with the receptor, or the cytotoxic effect on cells in complexes with the Hsp70 protein [34]. It has been shown that anti-TNF antibodies that reduce TNF levels result in a decrease in the development of rheumatoid arthritis and sepsis [28].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

Yurkina,

Romanova,

Tvorogova

et al. 2024

IJMS

View full text Add to dashboard Cite

Understanding the exact mechanisms of the activation of proinflammatory immune response receptors is very important for the targeted regulation of their functioning. In this work, we were able to identify the sites of the molecules in the proinflammatory cytokine TNF (tumor necrosis factor) and its TNFR1 (tumor necrosis factor receptor 1), which are necessary for the two-stage cytotoxic signal transduction required for tumor cell killing. A 12-membered TNFR1 peptide was identified and synthesized, interacting with the ligands of this receptor protein’s TNF and Tag7 and blocking their binding to the receptor. Two TNF cytokine peptides interacting with different sites of TNFR1 receptors were identified and synthesized. It has been demonstrated that the long 16-membered TNF peptide interferes with the binding of TNFR1 ligands to this receptor, and the short 6-membered peptide interacts with the receptor site necessary for the transmission of a cytotoxic signal into the cell after the ligands’ interaction with the binding site. This study may help in the development of therapeutic approaches to regulate the activity of the cytokine TNF.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

Yurkina,

Romanova,

Tvorogova

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Interestingly, Mts1 and Hsp70 compete for binding to Tag7. An excess of Mts1 displaces Hsp70 from the Tag7-Hsp70 complex to form a Tag7-Mts1 complex devoid of cytotoxic activity [ 22 ]. These results suggest that both proteins bind to the same site of the Tag7 molecule.…”

Section: Introductionmentioning

confidence: 99%

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

Yurkina,

Romanova,

Shcherbakov

et al. 2024

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…The next stage of the study was to evaluate the cytotoxic activity of the obtained complexes. It was previously shown that Tag7–Hsp70 and 17.1–Hsp70 complexes are cytotoxic [ 13 ]. As mentioned above, Tag7 is involved in the induction of cytotoxicity by interacting with the TNFR1 receptor, which induces alternative cytotoxic processes, apoptosis and necroptosis.…”

mentioning

confidence: 99%

HspBP1 in Complex with the Peptide of the Innate Immunity Protein Tag7 is Able to Lyse Tumor Cells Carrying TNFR1 Receptor

Romanova,

Yurkina,

Yashin

et al. 2024

Dokl Biochem Biophys

View full text Add to dashboard Cite

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 HspBP1 protein, 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 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.

show abstract

Short Peptides of Innate Immunity Protein Tag7 (PGLYRP1) Selectively Induce Inhibition or Activation of Tumor Cell Death via TNF Receptor

Cited by 4 publications

References 34 publications

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

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

HspBP1 in Complex with the Peptide of the Innate Immunity Protein Tag7 is Able to Lyse Tumor Cells Carrying TNFR1 Receptor

Contact Info

Product

Resources

About