MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance
Ilaria Moscetti,1 Emanuela Teveroni,2,3 Fabiola Moretti,3 Anna Rita Bizzarri,1 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, Department DEB, Università della Tuscia, Viterbo, Italy; 2Department of Endocrinology and Metabolism, Università Cattolica di Roma, Roma, I...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2016
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0946000f0c5343e38b52bf77d4f403ad |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0946000f0c5343e38b52bf77d4f403ad |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0946000f0c5343e38b52bf77d4f403ad2021-12-02T00:53:28ZMDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance1178-2013https://doaj.org/article/0946000f0c5343e38b52bf77d4f403ad2016-08-01T00:00:00Zhttps://www.dovepress.com/mdm2ndashmdm4-molecular-interaction-investigated-by-atomic-force-spect-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ilaria Moscetti,1 Emanuela Teveroni,2,3 Fabiola Moretti,3 Anna Rita Bizzarri,1 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, Department DEB, Università della Tuscia, Viterbo, Italy; 2Department of Endocrinology and Metabolism, Università Cattolica di Roma, Roma, Italy; 3Institute of Cell Biology and Neurobiology, Consiglio Nazionale delle Ricerche (CNR), Roma, Italy 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. Keywords: MDM2, MDM4, atomic force spectroscopy, surface plasmon resonanceMoscetti ITeveroni EMoretti FBizzarri ARCannistraro SDove Medical PressarticleMDM2MDM4Atomic Force SpectroscopySurface Plasmon Resonance.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4221-4229 (2016) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
MDM2 MDM4 Atomic Force Spectroscopy Surface Plasmon Resonance. Medicine (General) R5-920 |
| spellingShingle |
MDM2 MDM4 Atomic Force Spectroscopy Surface Plasmon Resonance. Medicine (General) R5-920 Moscetti I Teveroni E Moretti F Bizzarri AR Cannistraro S MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| description |
Ilaria Moscetti,1 Emanuela Teveroni,2,3 Fabiola Moretti,3 Anna Rita Bizzarri,1 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, Department DEB, Università della Tuscia, Viterbo, Italy; 2Department of Endocrinology and Metabolism, Università Cattolica di Roma, Roma, Italy; 3Institute of Cell Biology and Neurobiology, Consiglio Nazionale delle Ricerche (CNR), Roma, Italy 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. Keywords: MDM2, MDM4, atomic force spectroscopy, surface plasmon resonance |
| format |
article |
| author |
Moscetti I Teveroni E Moretti F Bizzarri AR Cannistraro S |
| author_facet |
Moscetti I Teveroni E Moretti F Bizzarri AR Cannistraro S |
| author_sort |
Moscetti I |
| title |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| title_short |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| title_full |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| title_fullStr |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| title_full_unstemmed |
MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| title_sort |
mdm2–mdm4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/0946000f0c5343e38b52bf77d4f403ad |
| work_keys_str_mv |
AT moscettii mdm2ndashmdm4molecularinteractioninvestigatedbyatomicforcespectroscopyandsurfaceplasmonresonance AT teveronie mdm2ndashmdm4molecularinteractioninvestigatedbyatomicforcespectroscopyandsurfaceplasmonresonance AT morettif mdm2ndashmdm4molecularinteractioninvestigatedbyatomicforcespectroscopyandsurfaceplasmonresonance AT bizzarriar mdm2ndashmdm4molecularinteractioninvestigatedbyatomicforcespectroscopyandsurfaceplasmonresonance AT cannistraros mdm2ndashmdm4molecularinteractioninvestigatedbyatomicforcespectroscopyandsurfaceplasmonresonance |
| _version_ |
1718403417326485504 |