p300/MDM2 Complexes Participate in MDM2-mediated p53 Degradation

Mol Cell. 1998 Oct;2(4):405-15. doi: 10.1016/s1097-2765(00)80140-9.

Abstract

Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • DNA-Binding Proteins*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oncogene Proteins, Viral / genetics
  • Protein Binding / physiology
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitins / metabolism

Substances

  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Ubiquitins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2