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

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

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211 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 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(1). 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.
Original languageEnglish
Pages (from-to)552 - 556
Number of pages5
JournalNature
Volume455
Issue number7212
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

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