Polyubiquitination of p53 by a Ubiquitin Ligase Activity of p300

@article{Grossman2003PolyubiquitinationOP,
  title={Polyubiquitination of p53 by a Ubiquitin Ligase Activity of p300},
  author={Steven R. Grossman and Maria Divina E Deato and Chrystelle Brignone and Ho Man Chan and Andrew L. Kung and Hideaki Tagami and Yoshihiro Nakatani and David M Livingston},
  journal={Science},
  year={2003},
  volume={300},
  pages={342 - 344}
}
Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300–CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression… 

Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2

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UBE4B, a ubiquitin chain assembly factor, is required for MDM2-mediated p53 polyubiquitination and degradation

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It is shown that the chaperone-associated ubiquitin ligase CHIP is able to induce the proteasomal degradation of p53, and that mutant and wild-type p53 transiently associate with molecular chaperones and can be diverted onto a degradation pathway through this association.

CBP and p300 are cytoplasmic E4 polyubiquitin ligases for p53

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p53 Ubiquitination and proteasomal degradation.

An in vitro degradation assay in which ubiquitinated p53 is incubated with purified 26S proteasomes can be used to provide insight into the biochemical nature of p53 ubiquitination and degradation.

The MDM2-p53 interaction.

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Cul4A Physically Associates with MDM2 and Participates in the Proteolysis of p53

Evidence is provided for a role of Cul4A in the MDM2-mediated proteolysis of p53 and for its role in the decay-rate and accumulation in response to DNA damage.

Regulation of the p53 tumor suppressor protein by Clycogen Synthase Kinase 3

It is concluded that GSK 3 regulates p53 levels by phosphorylating key sites in the central domain of the Mdm2 protein, which reveals a new mechanism for DNA damage-induced p53 accumulation and describes a post-ubiquitylation function of the H2O2 oncoprotein, the interaction of the mdm2protein with the proteasome.
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