Regulation of p53: TRIM24 enters the RING

Cell Cycle. 2009 Nov 15;8(22):3668-74. doi: 10.4161/cc.8.22.9979. Epub 2009 Nov 2.


Negative regulation of p53 in normal, unstressed cells maintains levels of this tumor suppressor below a threshold for cell cycle arrest or apoptosis, and is rapidly reversed in the face of cellular stresses to permit p53 response. Recently, we created a new mouse and stem cell model by knock-in addition of an epitope tag at Trp53. Biochemical purification of endogenous, tagged p53-protein complexes from mouse embryonic stem cells, and peptide analysis by mass spectrometry, revealed a new RING-domain E3-ubiquitin ligase TRIM24 that targets p53 for degradation. Depletion of TRIM24, formerly named TIF1alpha, in tumor-derived cells induces p53-dependent apoptosis. In Drosophila, bonus is a single copy gene homologous to the mammalian Tif1 family. Mosaic deletion of bonus induces cell death in vivo, which is rescued by depletion of D-p53. Bonus is the first identified regulator of p53 protein levels in Drosophila, which lacks an ortholog of Mdm2. TRIM24/bonus may be the ancestral precursor of the large group of mammalian E3-ligases that target p53 for ubiquitin modification. Understanding the specific roles that these numerous E3-ligases have in the hierarchy of p53-regulation remains a challenge for the field. We discuss various scenarios for selectivity in choice of E3-ligase targeting p53 for degradation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cell Cycle / genetics*
  • Drosophila
  • Drosophila Proteins / metabolism
  • Embryonic Stem Cells / enzymology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Mass Spectrometry
  • Mice
  • Models, Animal*
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*


  • Bon protein, Drosophila
  • Drosophila Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • transcriptional intermediary factor 1
  • Ubiquitin-Protein Ligases