Negatively charged metal oxide nanoparticles interact with the 20S proteasome and differentially modulate its biologic functional effects.
The multicatalytic ubiquitin-proteasome system (UPS) carries out proteolysis in a highly orchestrated way and regulates a large number of cellular processes. Deregulation of the UPS in many disorders has been documented. In some cases, such as carcinogenesis, elevated proteasome activity has been implicated in disease development, while the etiology of other diseases, such as neurodegeneration, includes decreased UPS activity. Therefore, agents that alter proteasome activity could suppress as well as enhance a multitude of diseases. Metal oxide nanoparticles, often developed as diagnostic tools, have not previously been tested as modulators of proteasome activity. Here, several types of metal oxide nanoparticles were found to adsorb to the proteasome and show variable preferential binding for particular proteasome subunits with several peptide binding "hotspots" possible. These interactions depend on the size, charge, and concentration of the nanoparticles and affect proteasome activity in a time-dependent manner. Should metal oxide nanoparticles increase proteasome activity in cells, as they do in vitro, unintended effects related to changes in proteasome function can be expected.
Feinberg School of Medicine, Department of Radiation Oncology, Northwestern University , Chicago, Illinois 60611, United States.
Christine A
CA
Falaschetti
Tatjana
T
Paunesku
Jasmina
J
Kurepa
Dhaval
D
Nanavati
Stanley S
SS
Chou
Mrinmoy
M
De
MinHa
M
Song
Jung-tak
JT
Jang
Aiguo
A
Wu
Vinayak P
VP
Dravid
Jinwoo
J
Cheon
Jan
J
Smalle
Gayle E
GE
Woloschak
D000838:Anions; D001665:Binding Sites; D004789:Enzyme Activation; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure*; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D055672:Static Electricity
D000838:Anions; D010087:Oxides; D046988:Proteasome Endopeptidase Complex