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

Erick J. Morris, Jun Yuan Ji, Fajun Yang, Luisa Di Stefano, Anabel Herr, Nam Sung Moon, Eun Jeong Kwon, Kevin M. Haigis, Anders M. Näär, Nicholas J. Dyson

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

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 β-catenin/T-cell factor (TCF)-dependent transcription, and that this function contributes to E2F1-induced apoptosis. E2F1 deregulation suppresses β-catenin activity in an adenomatous polyposis coli (APC)/glycogen synthase kinase-3 (GSK3)-independent manner, reducing the expression of key β-catenin targets including c-MYC. This interaction explains why colorectal tumours, which depend on β-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 β-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 β-catenin.

Original languageEnglish (US)
Pages (from-to)552-556
Number of pages5
JournalNature
Volume455
Issue number7212
DOIs
StatePublished - Sep 25 2008
Externally publishedYes

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Cyclin-Dependent Kinase 8
Catenins
TCF Transcription Factors
Colorectal Neoplasms
E2F1 Transcription Factor
Apoptosis
Tumor Suppressor Proteins
Glycogen Synthase Kinase 3
Retinoblastoma Protein
Adenomatous Polyposis Coli
Oncogene Proteins

ASJC Scopus subject areas

  • General

Cite this

Morris, E. J., Ji, J. Y., Yang, F., Di Stefano, L., Herr, A., Moon, N. S., ... Dyson, N. J. (2008). E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature, 455(7212), 552-556. https://doi.org/10.1038/nature07310

E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. / Morris, Erick J.; Ji, Jun Yuan; Yang, Fajun; Di Stefano, Luisa; Herr, Anabel; Moon, Nam Sung; Kwon, Eun Jeong; Haigis, Kevin M.; Näär, Anders M.; Dyson, Nicholas J.

In: Nature, Vol. 455, No. 7212, 25.09.2008, p. 552-556.

Research output: Contribution to journalArticle

Morris, EJ, Ji, JY, Yang, F, Di Stefano, L, Herr, A, Moon, NS, Kwon, EJ, Haigis, KM, Näär, AM & Dyson, NJ 2008, 'E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8', Nature, vol. 455, no. 7212, pp. 552-556. https://doi.org/10.1038/nature07310
Morris EJ, Ji JY, Yang F, Di Stefano L, Herr A, Moon NS et al. E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature. 2008 Sep 25;455(7212):552-556. https://doi.org/10.1038/nature07310
Morris, Erick J. ; Ji, Jun Yuan ; Yang, Fajun ; Di Stefano, Luisa ; Herr, Anabel ; Moon, Nam Sung ; Kwon, Eun Jeong ; Haigis, Kevin M. ; Näär, Anders M. ; Dyson, Nicholas J. / E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. In: Nature. 2008 ; Vol. 455, No. 7212. pp. 552-556.
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