pygopus Encodes a nuclear protein essential for wingless/Wnt signaling.
The Wingless (Wg)/Wnt signal transduction pathway regulates many developmental processes through a complex of Armadillo(Arm)/beta-catenin and the HMG-box transcription factors of the Tcf family. We report the identification of a new component, Pygopus (Pygo), that plays an essential role in the Wg/Wnt signal transduction pathway. We show that Wg signaling is diminished during embryogenesis and imaginal disc development in the absence of pygo activity. Pygo acts downstream or in parallel with Arm to regulate the nuclear function of Arm protein. pygo encodes a novel and evolutionarily conserved nuclear protein bearing a PHD finger that is essential for its activity. We further show that Pygo can form a complex with Arm in vivo and possesses a transcription activation domain(s). Finally, we have isolated a Xenopus homolog of pygo (Xpygo). Depletion of maternal Xpygo by antisense deoxyoligonucleotides leads to ventralized embryonic defects and a reduction of the expression of Wnt target genes. Together, these findings demonstrate that Pygo is an essential component in the Wg/Wnt signal transduction pathway and is likely to act as a transcription co-activator required for the nuclear function of Arm/beta-catenin.
Belenkaya
Tatyana Y
TY
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, OH 45229, USA.
Han
Chun
C
Standley
Henrietta J
HJ
Lin
Xinda
X
Houston
Douglas W
DW
Heasman
Janet
J
Lin
Xinhua
X
D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D019476:Insect Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D014981:Xenopus; D029961:Zebrafish Proteins
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C453400:pygo protein, Drosophila; C074622:wg protein, Drosophila