Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53

Cell Death Dis. 2015 May 21;6(5):e1764. doi: 10.1038/cddis.2015.117.


The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number of growth-arrest- and apoptosis-related genes. However, a clear understanding of which factor/s influences the choice between these two opposing p53-dependent outcomes remains largely elusive. We have previously described that in response to DNA damage, the RNA polymerase II-binding protein Che-1/AATF transcriptionally activates p53. Here, we show that Che-1 binds directly to p53. This interaction essentially occurs in the first hours of DNA damage, whereas it is lost when cells undergo apoptosis in response to posttranscriptional modifications. Moreover, Che-1 sits in a ternary complex with p53 and the oncosuppressor Brca1. Accordingly, our analysis of genome-wide chromatin occupancy by p53 revealed that p53/Che1 interaction results in preferential transactivation of growth arrest p53 target genes over its pro-apoptotic target genes. Notably, exposure of Che-1(+/-) mice to ionizing radiations resulted in enhanced apoptosis of thymocytes, compared with WT mice. These results confirm Che-1 as an important regulator of p53 activity and suggest Che-1 to be a promising yet attractive drug target for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • BRCA1 Protein / metabolism*
  • Cell Cycle Checkpoints / genetics*
  • Cell Line, Tumor
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Enzyme Activation / genetics
  • Gene Expression Regulation
  • HCT116 Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Transgenic
  • Protein Binding / genetics
  • RNA Interference
  • RNA, Small Interfering
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Thymocytes / pathology
  • Thymocytes / radiation effects
  • Transcriptional Activation / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • AATF protein, human
  • Apoptosis Regulatory Proteins
  • BRCA1 Protein
  • BRCA1 protein, human
  • RNA, Small Interfering
  • Repressor Proteins
  • Tumor Suppressor Protein p53

Associated data

  • GEO/GSE60267