Title |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance
|
---|---|
Published in |
International Journal of Nanomedicine, August 2016
|
DOI | 10.2147/ijn.s114705 |
Pubmed ID | |
Authors |
Ilaria Moscetti, Emanuela Teveroni, Fabiola Moretti, Anna Rita Bizzarri, Salvatore Cannistraro |
Abstract |
Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 3 | 75% |
Members of the public | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 3 | 23% |
Researcher | 3 | 23% |
Professor > Associate Professor | 2 | 15% |
Student > Master | 1 | 8% |
Student > Doctoral Student | 1 | 8% |
Other | 2 | 15% |
Unknown | 1 | 8% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 3 | 23% |
Agricultural and Biological Sciences | 2 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
Immunology and Microbiology | 1 | 8% |
Physics and Astronomy | 1 | 8% |
Other | 2 | 15% |
Unknown | 3 | 23% |