Identification of a Catalytic Active but Non-Aggregating MDM2 RING Domain Variant
نویسندگان
چکیده
منابع مشابه
Deconstructing nucleotide binding activity of the Mdm2 RING domain
Mdm2, a central negative regulator of the p53 tumor suppressor, possesses a Really Interesting New Gene (RING) domain within its C-terminus. In addition to E3 ubiquitin ligase activity, the Mdm2 RING preferentially binds adenine base nucleotides, and such binding leads to a conformational change in the Mdm2 C-terminus. Here, we present further biochemical analysis of the nucleotide-Mdm2 interac...
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In this study, we attempt to gain insights into the molecular mechanism underlying MDM2-mediated TGF-β resistance. MDM2 renders cells refractory to TGF-β by overcoming a TGF-β-induced G1 cell cycle arrest. Because the TGF-β resistant phenotype is reversible upon removal of MDM2, MDM2 likely confers TGF-β resistance by directly targeting the cellular machinery involved in the growth inhibition b...
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The MDM2 oncoprotein plays multiple regulatory roles in the control of p53-dependent gene expression. A picture of MDM2 is emerging where structurally discrete but interdependent functional domains are linked through changes in conformation. The domain structure includes: (i) a hydrophobic pocket at the N terminus of MDM2 that is involved in both its transrepressor and E3-ubiqutin ligase functi...
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The RING domain of MDM2 that is essential for its E3 ligase activity mediates binding to itself and its structural homologue MDMX. Whereas it has been reported that RING domain interactions are critical, it is not well understood how they affect the E3 ligase activity of MDM2. We report that the E3 ligase activity requires the RING domain-dependent complex formation. In vivo, MDM2 and MDMX hete...
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ژورنال
عنوان ژورنال: Journal of Molecular Biology
سال: 2021
ISSN: 0022-2836
DOI: 10.1016/j.jmb.2021.166807