Dynamics in the p53-Mdm2 ubiquitination pathway

Cell Cycle. 2004 Jul;3(7):895-9. Epub 2004 Jul 2.

Abstract

The tumor suppressor p53 is highly regulated under various states of cellular stress. p53 stability is predominantly regulated through the ubiquitin-proteasomal pathway by the E3 ligase Mdm2. p53 ubiquitination is a dynamic process with Mdm2 capable of catalyzing both mono- and polyubiquitination. Additionally, deubiquitination is an important step occurring in p53 and Mdm2 stabilities. Factors such as HAUSP, p14(ARF), and MdmX play important regulatory roles in p53 ubiquitination/deubiquitination and their interplay with Mdm2 and p53 compound layers of complexity for regulating this important pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Humans
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Signal Transduction / physiology*
  • Tumor Suppressor Protein p14ARF / genetics
  • Tumor Suppressor Protein p14ARF / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7

Substances

  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • Ubiquitin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Endopeptidases
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7
  • Proteasome Endopeptidase Complex