Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 11, Pages 4092-4097Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109131109
Keywords
polyubiquitin chain; radiation sensitization; SUMO-binding motif (SBM); SUMO-interacting motif (SIM)
Categories
Funding
- AMMI
- NIH [R01GM074748, R01GM086171]
- National Cancer Institute [P30 CA33572]
- [F32CA134180]
Ask authors/readers for more resources
Protein-protein interactions mediated by ubiquitin-like (Ubl) modifications occur as mono-Ubl or poly-Ubl chains. Proteins that regulate poly-SUMO (small ubiquitin-like modifier) chain conjugates play important roles in cellular response to DNA damage, such as those caused by cancer radiation therapy. Additionally, high atomic number metals, such as gold, preferentially absorb much more X-ray energy than soft tissues, and thus augment the effect of ionizing radiation when delivered to cells. In this study, we demonstrate that conjugation of a weak SUMO-2/3 ligand to gold nanoparticles facilitated selective multivalent interactions with poly-SUMO-2/3 chains leading to efficient inhibition of poly-SUMO-chain-mediated protein-protein interactions. The ligand-gold particle conjugate significantly sensitized cancer cells to radiation but was not toxic to normal cells. This study demonstrates a viable approach for selective targeting of poly-Ubl chains through multivalent interactions created by nanoparticles that can be chosen based on their properties, such as abilities to augment radiation effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available