A small lipidated peptide that inhibits transferrin uptake
- 1Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY 14203 USA
- 2Program for Neuroscience, University at Buffalo - The State University of New York, Buffalo, NY 14203 USA
Abstract
The transferrin receptor (TfR) is a transmembrane glycoprotein that plays a crucial role in iron uptake. TfR is often overexpressed in malignant cancer cells, enabling rapid proliferation. Given the significance of iron uptake in various disease states, blocking transferrin (Tf)-mediated iron uptake could serve as an effective therapeutic strategy. Tf-TfR endocytosis is facilitated by the multimeric AP2 complex through a tyrosine motif on TfR, which is recognized by the AP2 mu subunit. In the present study, fluorescently labeled transferrin was employed to monitor cellular endocytosis in the presence of lipidated decoy peptides containing endocytic motifs that are recognized by the AP2 complex. The results demonstrated that transferrin endocytosis is inhibited when in the presence of a peptide that specifically targets the mu subunit, but not with a peptide that targets the sigma subunit. These findings suggest that Tf-TfR endocytosis can be selectively inhibited through the selective inhibition of the AP2 mu subunit, indicating potential as a novel strategy for inhibiting iron influx in malignant cancer cells.
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BibTeX
@article{nicosia2026small,
title = {{A small lipidated peptide that inhibits transferrin uptake}},
author = {Richard Nicosia and Arin Bhattacharjee},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-64148-w},
url = {https://doi.org/10.1038/s41598-026-64148-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A small lipidated peptide that inhibits transferrin uptake
AU - Richard Nicosia
AU - Arin Bhattacharjee
PY - 2026
DA - 2026/07/27
JO - Scientific Reports
DO - 10.1038/s41598-026-64148-w
UR - https://doi.org/10.1038/s41598-026-64148-w
AB - The transferrin receptor (TfR) is a transmembrane glycoprotein that plays a crucial role in iron uptake. TfR is often overexpressed in malignant cancer cells, enabling rapid proliferation. Given the significance of iron uptake in various disease states, blocking transferrin (Tf)-mediated iron uptake could serve as an effective therapeutic strategy. Tf-TfR endocytosis is facilitated by the multimeric AP2 complex through a tyrosine motif on TfR, which is recognized by the AP2 mu subunit. In the present study, fluorescently labeled transferrin was employed to monitor cellular endocytosis in the presence of lipidated decoy peptides containing endocytic motifs that are recognized by the AP2 complex. The results demonstrated that transferrin endocytosis is inhibited when in the presence of a peptide that specifically targets the mu subunit, but not with a peptide that targets the sigma subunit. These findings suggest that Tf-TfR endocytosis can be selectively inhibited through the selective inhibition of the AP2 mu subunit, indicating potential as a novel strategy for inhibiting iron influx in malignant cancer cells.
SN - 2045-2322
ER -