Smad Ubiquitylation Regulatory Factor 1/2 (Smurf1/2) Promotes p53 Degradation by Stabilizing the E3 Ligase MDM2*

@article{Nie2010SmadUR,
  title={Smad Ubiquitylation Regulatory Factor 1/2 (Smurf1/2) Promotes p53 Degradation by Stabilizing the E3 Ligase MDM2*},
  author={J. Nie and P. Xie and L. Liu and G. Xing and Z. Chang and Yuxin Yin and Chunyan Tian and F. He and Lingqiang Zhang},
  journal={The Journal of Biological Chemistry},
  year={2010},
  volume={285},
  pages={22818 - 22830}
}
The tumor suppressor p53 protein is tightly regulated by a ubiquitin-proteasomal degradation mechanism. Several E3 ubiquitin ligases, including MDM2 (mouse double minute 2), have been reported to play an essential role in the regulation of p53 stability. However, it remains unclear how the activity of these E3 ligases is regulated. Here, we show that the HECT-type E3 ligase Smurf1/2 (Smad ubiquitylation regulatory factor 1/2) promotes p53 degradation by enhancing the activity of the E3 ligase… Expand
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References

SHOWING 1-10 OF 50 REFERENCES
Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.
TLDR
The data indicate that the MDM2-p53 physical interaction, without Mdm2-mediated p53 ubiquitination, cannot control p53 activity sufficiently to allow early mouse embryonic development, and (2) Mdm1's E3 function is not required for Mdm 2 degradation. Expand
Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53*
TLDR
Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger, and it is shown that Mdm2 mediates its own ubiquitination in a Ringing finger-dependent manner, which requires no eukaryotic proteins other than ubiquitIn-activating enzyme (E1) and an ubiquit in-conjugating enzyme(E2). Expand
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1
TLDR
Findings provide evidence that the WW domains linker is important in complex assembly and in regulating activity of HECT-type E3s and that CKIP-1 functions as the first auxiliary factor to enhance the activation of Smurf1. Expand
Mdm2 promotes the rapid degradation of p53
TLDR
It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal. Expand
Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans
TLDR
The crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 are reported and it is shown that these residues are part of an extended surface that is essential for ubiquitylation in trans. Expand
The p53-Mdm2 module and the ubiquitin system.
TLDR
The p53 tumor suppressor protein is a short-lived protein, which is stabilized in response to cellular stress, and the exact site of degradation of p53 is presently under debate. Expand
Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation
TLDR
Pirh2, a gene regulated by p53 that encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity, is described and it is proposed that Pirh2 is involved in the negative regulation of p53 function through physical interaction and ubiquit in-mediated proteolysis. Expand
Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1
TLDR
Findings identify the first instance of a ubiquitin ligase that causes stabilization of p53 while inactivating its transcriptional activities, and point to a possible feedback loop mechanism. Expand
ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways
TLDR
It is shown that ARF binds to MDM2 and promotes the rapid degradation of MDM 2, and deletion of the ARF-INK4a locus simultaneously impairs both the INK4a-cyclin D/CDK4-RB and the ARf-MDM2-p53 pathways. Expand
Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53
TLDR
MDM2 and MDM4 are nonoverlapping critical regulators of p53 in vivo, which define a new pathway of p 53 regulation and raise the possibility that increasedMDM4 levels and the resulting inactivation of p52 contribute to the development of human tumors. Expand
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