Mouse double minute 2 homolog mRNA (MDM2 mRNA) (MDM2 mRNA)

Mouse double minute 2 homolog (MDM2) mRNA is the transcript encoding the MDM2 protein, which serves as the principal negative regulator of the p53 tumor suppressor [UniProt P22301]. The MDM2 protein functions as an E3 ubiquitin ligase that binds to the p53 transactivation domain, promoting its ubiquitination and subsequent degradation by the proteasome [Momand et al., 1992]. In many human cancers, including soft tissue sarcomas and glioblastomas, the MDM2 gene is amplified or the mRNA is overexpressed, leading to the suppression of p53-mediated cell cycle arrest and apoptosis [Bond et al., 2005]. Targeting the MDM2 mRNA transcript using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) is a therapeutic strategy designed to prevent the synthesis of the MDM2 protein entirely [Zhang et al., 2005]. By reducing MDM2 protein levels, these RNA-targeted therapies facilitate the stabilization and accumulation of wild-type p53, thereby restoring its tumor-suppressive functions [Wang et al., 2011]. This mechanism is distinct from small-molecule inhibitors that block the MDM2-p53 protein-protein interaction, as it addresses the total protein burden within the cell [Nag et al., 2013]. Clinical development of MDM2 mRNA-targeting agents has faced challenges, including the need for effective delivery systems and the management of on-target toxicities related to p53 activation in normal tissues [Iancu-Rubin et al., 2014]. Despite these challenges, MDM2 mRNA remains a high-interest target for precision oncology, particularly in tumors with wild-type p53 and MDM2 amplification [Khoo et al., 2014].

Other names

MDM2 messenger RNAHDM2 mRNAE3 ubiquitin-protein ligase Mdm2 mRNADouble minute 2 protein mRNA

Antisense-mediated mRNA degradation (RNase H-dependent) or RNA interference (RNAi) leading to reduced MDM2 protein synthesis and subsequent p53 stabilization.