Mdm2 binds p73 alpha without targeting degradation

Oncogene. 1999 Jul 8;18(27):3923-9. doi: 10.1038/sj.onc.1202781.

Abstract

The function of the p53 tumor suppressor protein is regulated by interaction with Mdm2, which targets p53 for ubiquitin dependent degradation. We show here that like p53, p73 alpha forms an interaction with Mdm2, both in vitro and in cells, but this does not result in the degradation of the p73 alpha protein. The human papillomavirus E6 protein also fails to degrade p73 alpha, suggesting that the mechanisms governing p73 alpha stability are distinct from those known to regulate p53 stability. However, the interaction of Mdm2 with 73 alpha is sufficient to impede p73 alpha transcriptional function, despite the lack of degradation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Tumor Suppressor
  • Humans
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oncogene Proteins, Viral / physiology
  • Osteosarcoma
  • Papillomaviridae
  • Proteasome Endopeptidase Complex
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-mdm2
  • Repressor Proteins / physiology
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Proteins

Substances

  • Cysteine Proteinase Inhibitors
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • Multienzyme Complexes
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • p73 protein, human
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex