Abstract
MDM2 oncogenic protein is the principal cellular antagonist of the p53 tumor suppresser gene. p53 activity needs exquisite control to elicit appropriate responses to differential cellular stress conditions. p53 becomes stabilized and active upon various types of stresses. However, too much p53 is not beneficial to cells and causes lethality. At the steady state, p53 activity needs to be leashed for cell survival. Early studies suggested that the MDM2 oncoprotein negatively regulates p53 activity through the induction of p53 protein degradation. MDM2 serves as an E3 ubiquitin ligase of p53; it catalyzes polyubiquitination and subsequently induces proteasome degradation to downregulate p53 protein level. However, the mechanism by which MDM2 represses p53 is not a single mode. Emerging evidence reveals another cellular location of MDM2-p53 interaction. MDM2 is recruited to chromatin, specifically the p53 responsive promoter regions, in a p53 dependent manner. MDM2 is proposed to directly inhibit p53 transactivity at chromatin. This article provides an overview of the mechanism by which p53 is repressed by MDM2 in both ubiquitination dependent and ubiquitination independent pathways.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
