Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation

Daniele Bergamaschi; Yardena Samuels; Shan Zhong; Xin Lu

doi:10.1038/sj.onc.1208535

Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation

Oncogene. 2005 May 26;24(23):3836-41. doi: 10.1038/sj.onc.1208535.

Authors

Daniele Bergamaschi¹, Yardena Samuels, Shan Zhong, Xin Lu

Affiliation

¹ Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London W1W 7BS, UK.

PMID: 15782125
DOI: 10.1038/sj.onc.1208535

Abstract

Using various mutants of p53 and mdm2, we demonstrate here that both the DNA binding and transactivation function of p53 are required for ASPP1 and ASPP2 to stimulate the apoptotic functions of p53. Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53. Importantly, mdm2 and mdmx can prevent the stimulatory effects of ASPP1 and ASPP2 without targeting p53 for degradation. These data provide a novel mechanism by which mdm2 and mdmx act as potent inhibitors of p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Apoptosis
Apoptosis Regulatory Proteins
Carrier Proteins / physiology*
Cell Cycle Proteins
DNA / metabolism
Humans
Nuclear Proteins / physiology*
Proto-Oncogene Proteins / physiology*
Proto-Oncogene Proteins c-mdm2
Transcriptional Activation
Tumor Suppressor Protein p53 / antagonists & inhibitors*
Tumor Suppressor Protein p53 / physiology

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
Carrier Proteins
Cell Cycle Proteins
MDM4 protein, human
Nuclear Proteins
PPP1R13B protein, human
Proto-Oncogene Proteins
TP53BP2 protein, human
Tumor Suppressor Protein p53
DNA
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2