Mediator Is a Transducer of Wnt/β-Catenin Signaling*

By Seokjoong Kim, Xuan Xu, A. Hecht, T. Boyer. Journal of Biological Chemistry, 2006

250 citations recorded by the source corpus.

Signal transduction within the canonical Wnt/β-catenin pathway drives development and carcinogenesis through programmed or unprogrammed changes in gene transcription. Although the upstream events linked to signal-induced activation of β-catenin in the cytoplasm have been deciphered in considerable detail, much less is known regarding the mechanism by which β-catenin stimulates target gene transcription in the nucleus. Here, we show that β-catenin physically and functionally targets the MED12 subunit in Mediator to activate transcription. The β-catenin transactivation domain bound directly to isolated MED12 and intact Mediator both in vitro and in vivo, and Mediator was recruited to Wnt-responsive genes in a β-catenin-dependent manner. Disruption of the β-catenin/MED12 interaction through dominant-negative interference- or RNA interference-mediated MED12 suppression inhibited β-catenin transactivation in response to Wnt signaling. This study thus identifies the MED12 interface within Mediator as a new component and a potential therapeutic target in the Wnt/β-catenin pathway.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/43a68bf0655cb1ecb9cc1884e774a74b592162f3

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Citations in the corpus

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation (2010, background): “Direct interactions of Mediator with mammalian β-catenin, leading to activation of target genes, have also been demonstrate”
The many faces and functions of β‐catenin (2012, unknown): “Then, the Mediator complex initiates the assembly of the RNApolII pre-initiation complex, accompanied by the binding of the Paf1 complex component Paraﬁbromin/ Hyrax (Kim et al , 2006; Mosimann et al , 2006; Parker et al , 2008).”
β-Catenin hits chromatin: regulation of Wnt target gene activation (2009, background): “Mediator complex subunit 12 ( MED12 ) binds directly to R12–C in vitro and positively promotes Wnt reporter activatio”