Poly(ADP-ribose) polymerase-1 is a component of the oncogenic T-cell factor-4/beta-catenin complex

Gastroenterology. 2005 Jun;128(7):1919-36. doi: 10.1053/j.gastro.2005.03.007.


Background & aims: T-cell factor (TCF)-4 regulates a certain set of genes related to growth and differentiation of intestinal epithelial cells. Aberrant transactivation of these TCF-4-regulated genes by beta-catenin protein plays a crucial role in early intestinal carcinogenesis, and the transcriptional machinery of the TCF-4/beta-catenin complex is likely to contain targets for molecular therapy. We explored the molecular composition of the TCF-4/beta-catenin transcriptional complex by means of proteomics.

Methods & results: A protein of approximately 112 kilodaltons was consistently coimmunoprecipitated with FLAG-tagged TCF-4 transiently expressed in HEK293 cells, and the protein was identified by mass spectrometry as poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 physically interacted with TCF-4 and augmented the transcriptional activity of the beta-catenin/TCF-4 complex. Knockdown of PARP-1 by RNA interference significantly suppressed both transcriptional activity and proliferation by colorectal cancer cells. Auto-polyADP-ribosylation of the PARP-1 protein induced by DNA damage inhibited the functional interaction of PARP-1 with TCF-4. PARP-1 was overexpressed in the intestinal adenomas of patients with familial adenomatous polyposis and multiple intestinal polyposis mice. The expression of PARP-1 was closely associated with the accumulation of beta-catenin and with the undifferentiated status of intestinal epithelial cells.

Conclusions: In this study, we identified PARP-1 as a novel coactivator of the beta-catenin/TCF-4 complex. Although PARP-1 has been believed to play a protective role against carcinogenesis, these expression patterns and functional properties of PARP-1 were highly suggestive of its participation in early colorectal carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation*
  • Humans
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / biosynthesis
  • Poly(ADP-ribose) Polymerases / physiology*
  • Proteomics
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • TCF Transcription Factors
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / biosynthesis
  • Transcription Factors / physiology*
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Tcf7l2 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases