Mdm2 has been identified as a p53 interacting protein that represses p53 transcriptional activity. Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53. Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53.

MDM2 targets p53 for ubiquitination and degradation by the proteasome –, shuttles p53 out of the nucleus,, prevents p53 from interacting with transcriptional co-activators, and recruits transcriptional co-repressors to p53 –.

Note that the p53-p300 interaction is enhanced in the Mdm2 m/m MEFs compared to Mdm2-null MEFs despite similar immunoprecipitation of p53 and equivalent loading for p300.. Discussion. This work provides further evidence that Mdm2 harboring a point mutation that abrogates its E3 ubiquitin ligase activity without affecting Mdm2-p53 binding is …

Jun 5, 2009 · Recent reports provide novel important insights into Mdm2-mediated regulation of p53 and how the physical and functional interactions between these two proteins are regulated. Moreover, a...

In unstressed cells, MDM2 constantly monoubiquitinates p53 and thus is the critical step in mediating its degradation by nuclear and cytoplasmic proteasomes. The interaction between p53 and MDM2 is conformation-based and is tightly regulated on multiple levels.

The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein …

May 13, 2024 · Mousedouble minute 2 (MDM2) is one of the molecules activated by p53 and plays an important role in the regulation of p53. MDM2 is generally believed to function as a negative regulator of p53 by facilitating its ubiquitination and subsequent degradation.

Jul 10, 2020 · Targeting the interaction between tumor suppressor p53 and the E3 ligase MDM2 represents an attractive treatment approach for cancers with wild-type or functional TP53.

Feb 1, 2003 · The inhibition of the p53–MDM2 interaction is an attractive strategy to activate p53-mediated apoptosis in tumours with overexpressed MDM2, but wild-type p53.

4 days ago · p53 is a tumor suppressor gene and is regarded as one of the most crucial genes in protecting humans against cancer. The protein Mdm2 and its homolog MdmX serve as negative regulators of p53. In nearly half of cancer cells, there is an overexpression of Mdm2 and MdmX, which inhibit p53 activity. Furthermore, Mdm2’s E3 ubiquitin ligase activity promotes the ubiquitination and degradation of p53.