Document
type: Class

Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions
type: Article
has funding vehicle: Consejo Nacional de Ciencia y Tecnología, CONACYT: 327879
related by: authorship_27545
related by: authorship_27542
type: Thing
origen: scopus
has publication venue: Molecular and Cellular Biology
type: Document
issue: 15
page end: 2205
volume: 36
related by: authorship_27546
related by: authorship_27540
e iscopus: 2-s2.0-84982853982
related by: authorship_27543
page start: 2195
type: Continuant
date time value: article date 4695
accesstype: All Open Access, Bronze, Green
crisid: 4695
chemicalscas: Ataxia Telangiectasia Mutated Proteins; ATM protein, human; MDM2 protein, human; MDM4 protein, human; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; RNA, Messenger; TP53 protein, human; Tumor Suppressor Protein p53
estado: published
related by: authorship_27538
type: Entity
doi: 10.1128/MCB.00113-16
freetext keyword: messenger RNA; protein HDMX; protein MDM2; protein p53; ubiquitin protein ligase E3; unclassified drug; zinc finger protein; ATM protein; ATM protein, human; MDM2 protein, human; MDM4 protein, human; messenger RNA; nuclear protein; oncoprotein; protein MDM2; protein p53; TP53 protein, human; allosterism; Article; circular dichroism; controlled study; DNA damage; enzyme specificity; human; nonhuman; priority journal; protein conformation; protein degradation; protein modification; protein phosphorylation; protein processing; protein protein interaction; protein purification; RING finger motif; ubiquitination; zinc finger motif; allosterism; animal; chemistry; enzyme specificity; genetics; metabolism; phosphorylation; protein domain; protein unfolding; Allosteric Regulation; Animals; Ataxia Telangiectasia Mutated Proteins; Humans; Nuclear Proteins; Phosphorylation; Protein Domains; Protein Unfolding; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; RNA, Messenger; Substrate Specificity; Tumor Suppressor Protein p53
abstract: HDM2 and HDMX are key negative regulatory factors of the p53 tumor suppressor under normal conditions by promoting its degradation or preventing its trans activity, respectively. It has more recently been shown that both proteins can also act as positive regulators of p53 afterDNAdamage. This involves phosphorylation byATMon serine residues HDM2(S395) and HDMX(S403), promoting their respective interaction with the p53 mRNA. However, the underlying molecular mechanisms of how these phosphorylation events switch HDM2 and HDMX from negative to positive regulators of p53 is not known. Our results show that these phosphorylation events reside within intrinsically disordered domains and change the conformation of the proteins. The modifications promote the exposition of N-terminal interfaces that support the formation of a new HDMX-HDM2 heterodimer independent of the C-terminal RING-RING interaction. The E3 ubiquitin ligase activity of this complex toward p53 is prevented by the p53 mRNA ligand but, interestingly, does not affect the capacity to ubiquitinate HDMX and HDM2. These results show how ATM-mediated modifications of HDMX and HDM2 switch HDM2 E3 ubiquitin ligase activity away from p53 but toward HDMX and itself and illustrate how the substrate specificity of HDM2 E3 ligase activity is regulated. © 2016, American Society for Microbiology.
related by: authorship_27541
most specific type: Article
related by: authorship_27544
type: Generically Dependent Continuant
type: Information Content Entity
most specific type: Document
pmid: 27215386
has funding vehicle: M14S01
related by: authorship_27539

Consejo Nacional de Ciencia y Tecnología, CONACYT: 327879
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type: BFO_0000020
type: Entity
type: Thing
type: Grant
type: Continuant
funding vehicle for: Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions

Continuant
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M14S01
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type: BFO_0000020
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type: Thing
type: Grant
type: Continuant
funding vehicle for: Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions

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Generically Dependent Continuant
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Molecular and Cellular Biology
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type: Document
type: Periodical
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type: Information Content Entity
type: Continuant
publication venue for: Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions

RDF description of Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions - http://orbis.uaslp.mx/vivo/individual/scopus4694
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date: 2026-08-28T04:04:57
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