E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8

Nature. 2008 Sep 25;455(7212):552-6. doi: 10.1038/nature07310. Epub 2008 Sep 14.


The E2F1 transcription factor can promote proliferation or apoptosis when activated, and is a key downstream target of the retinoblastoma tumour suppressor protein (pRB). Here we show that E2F1 is a potent and specific inhibitor of beta-catenin/T-cell factor (TCF)-dependent transcription, and that this function contributes to E2F1-induced apoptosis. E2F1 deregulation suppresses beta-catenin activity in an adenomatous polyposis coli (APC)/glycogen synthase kinase-3 (GSK3)-independent manner, reducing the expression of key beta-catenin targets including c-MYC. This interaction explains why colorectal tumours, which depend on beta-catenin transcription for their abnormal proliferation, keep RB1 intact. Remarkably, E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1. Thus, by retaining RB1 and amplifying CDK8, colorectal tumour cells select conditions that collectively suppress E2F1 and enhance the activity of beta-catenin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism
  • Apoptosis
  • Cell Line
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases / metabolism*
  • E2F1 Transcription Factor / antagonists & inhibitors*
  • E2F1 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Genes, myc / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Signal Transduction
  • TCF Transcription Factors / metabolism
  • Transcription, Genetic*
  • Wnt Proteins / metabolism
  • beta Catenin / antagonists & inhibitors*
  • beta Catenin / metabolism*


  • Adenomatous Polyposis Coli Protein
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Retinoblastoma Protein
  • TCF Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases
  • Glycogen Synthase Kinase 3