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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Armadillo Domain Proteins
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology
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Cell Line
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / physiopathology
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / anatomy & histology
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Drosophila melanogaster / embryology
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Drosophila melanogaster / genetics*
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Gene Expression Regulation, Developmental
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Humans
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Insect Proteins / genetics
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Insect Proteins / metabolism*
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Intracellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phenotype
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sequence Alignment
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Signal Transduction / physiology*
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Trans-Activators*
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Transcription Factors
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Transcription, Genetic
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Wnt1 Protein
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beta Catenin
Substances
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ARM protein, Drosophila
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Adaptor Proteins, Signal Transducing
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Armadillo Domain Proteins
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CTNNB1 protein, human
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Carrier Proteins
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Cytoskeletal Proteins
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Drosophila Proteins
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Insect Proteins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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PYGO1 protein, human
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PYGO2 protein, human
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Proto-Oncogene Proteins
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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Wnt1 Protein
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beta Catenin
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pygo protein, Drosophila
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wg protein, Drosophila