Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53
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چکیده
منابع مشابه
Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.
It is believed that Mdm2 suppresses p53 in two ways: transcriptional inhibition by direct binding, and degradation via its E3 ligase activity. To study these functions physiologically, we generated mice bearing a single-residue substitution (C462A) abolishing the E3 function without affecting p53 binding. Unexpectedly, homozygous mutant mice died before E7.5, and deletion of p53 rescued the let...
متن کاملHuman RING finger protein ZNF645 is a novel testis-specific E3 ubiquitin ligase.
A large number of testis-specific genes are involved in the complex process of mammalian spermatogenesis. Identification of these genes and their roles is important for understanding the mechanisms underlying spermatogenesis. Here we report on a novel human RING finger protein, ZNF645, which contains a C3HC4 RING finger domain, a C2H2 zinc-finger domain, and a proline-rich region, indicating th...
متن کاملRNF125 is a ubiquitin-protein ligase that promotes p53 degradation.
BACKGROUND/AIMS Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53. METHODS AND RESULTS RNF125 physically interacted with p53...
متن کاملThe Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity.
Mdm2, a key negative regulator of the p53 tumor suppressor, is a RING-type E3 ubiquitin ligase. The Mdm2 RING domain can be biochemically fractionated into two discrete species, one of which exists as higher order oligomers that are visible by electron microscopy, whereas the other is a monomer. Both fractions are ATP binding and E3 ligase activity competent, although the oligomeric fraction ex...
متن کاملAssociation of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53.
We have demonstrated previously that the oncoprotein Mdm2 has a ubiquitin ligase activity for the tumor suppressor p53 protein. In the present study, we characterize this ubiquitin ligase activity of Mdm2. We first demonstrate the ubiquitination of several p53 point mutants and deletion mutants by Mdm2. The point mutants, which cannot bind to Mdm2, are not ubiquitinated by Mdm2. The ubiquitinat...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2000
ISSN: 0021-9258
DOI: 10.1074/jbc.275.12.8945