title: Dual function of MDM2 and MDMX toward the tumor suppressors p53 and RB.
abstract: The orchestrated crosstalk between the retinoblastoma (RB) and p53 pathways contributes to preserving proper homeostasis within the cell. The deregulation of one or both pathways is a common factor in the development of most types of human cancer. The proto-oncoproteins MDMX and MDM2 are the main regulators of the well- known tumor suppressor p53 protein. Under normal conditions, MDM2 and MDMX inhibit p53, either via repression of its transcriptional activity by protein-protein interaction, or via polyubiquitination as a result of MDM2-E3 ubiquitin ligase activity, for which MDM2 needs to dimerize with MDMX. Under genotoxic stress conditions, both become positive regulators of p53. The ATM-dependent phosphorylation of MDM2 and MDMX allow them to bindp53mRNA, these interactions promote p53 translation. MDM2 and MDMX are also being revealed as effective regulators of the RB protein. MDM2 is able to degrade RB by two different mechanisms, that is, by ubiquitin dependent and independent pathways. MDMX enhances the ability of MDM2 to bind and degrade RB protein. However, MDMX also seems to stabilize RB through interaction and competition with MDM2. Here, we will contextualize the findings that suggest that the MDM2 and MDMX proteins have a dual function on both p53 and RB.
authors.affiliation: Instituto de Física, Universidad Autónoma de San Luis Potosí, Av Manuel Nava No 6 Zona Universitaria CP 78290. SLP, México.
authors.forename: Jesús
authors.initials: J
authors.lastname: Hernández-Monge
authors.affiliation: Instituto de Física, Universidad Autónoma de San Luis Potosí, Av Manuel Nava No 6 Zona Universitaria CP 78290. SLP, México.
authors.forename: Adriana Berenice
authors.initials: AB
authors.lastname: Rousset-Roman
authors.affiliation: Instituto de Física, Universidad Autónoma de San Luis Potosí, Av Manuel Nava No 6 Zona Universitaria CP 78290. SLP, México.
authors.forename: Ixaura
authors.initials: I
authors.lastname: Medina-Medina
authors.affiliation: Instituto de Física, Universidad Autónoma de San Luis Potosí, Av Manuel Nava No 6 Zona Universitaria CP 78290. SLP, México.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Olivares-Illana
keywords: MDM2; MDMX; RB; p53