A new nuclear component of the Wnt signalling pathway

Abstract

The Wnt signalling pathway is pivotal in normal and malignant development. A key effector is Armadillo (Arm)/beta-catenin, which functions with TCF to transcribe Wnt target-genes. Here, we report the discovery of pygopus (pygo), whose mutant phenotypes specifically mimic loss-of-Wingless (Wg) signalling. pygo is required for dTCF-mediated transcription, but not for Wg-induced stabilization of Arm. Pygo is a nuclear protein that is found in a complex with Arm in vivo. Humans possess two Pygo proteins, both of which are required for TCF-mediated transcription in colorectal cancer cells. The presence of a PHD domain implicates Pygo proteins in a chromatin-related function, and we propose that they mediate chromatin access to TCF or Arm/beta-catenin.

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

“…The higher levels of hPygo2 observed in HPV-infected cells and tissues suggested that it may, as in other cancers (2)(3)(4)(5)(6)39), have an important function in cervical cancer. HEN16T cells were therefore transfected with 2 siRNAs directed against hPygo2, siPy2-X, targeting its 3 0 -UTR and siPy2-Z targeting the coding region to determine the requirement of hPygo2.…”

Wnt signaling in disease and in development

“…Further interactions between the β-catenin-TCF complex and chromatin could be mediated by Legless (Bcl9) and Pygopos [29][30][31]. Mutations in either of these genes result in wingless-like phenotypes in Drosophila, and both genes promote Wnt signaling in mammalian cell culture experiments [30].…”

“…Mutations in either of these genes result in wingless-like phenotypes in Drosophila, and both genes promote Wnt signaling in mammalian cell culture experiments [30].…”

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

“…It was identified through its association with BCL9/Legless, which binds to b-catenin ( Fig. 2A; Kramps et al 2002;Thompson et al 2002;Hoffmans and Basler 2004;Townsley et al 2004;Li et al 2007). That said, Pygo can also directly interact with TCFs in a Wnt-independent manner, where it appears to serve as a histone methylation reader and context-dependent LEF/ TCF anti-repressor to facilitate subsequent Wnt-dependent transcription (de la Roche and Bienz 2007;Mieszczanek et al 2008;Gu et al 2013).…”