Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation
Autor: | Whitney M. Jones, Anna T. Chao, Michael Zavortink, Robert Saint, Amy Bejsovec |
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Rok vydání: | 2010 |
Předmět: |
Beta-catenin
GTPase-activating protein Cell Wnt1 Protein Biology Genes Reporter Transcription (biology) Two-Hybrid System Techniques medicine Animals Drosophila Proteins Humans Wings Animal Transcription factor Molecular Biology Cells Cultured beta Catenin Research Articles Body Patterning Cytokinesis Armadillo Domain Proteins Cell Nucleus Effector GTPase-Activating Proteins Wnt signaling pathway LRP6 LRP5 Epistasis Genetic Cell Biology Cell biology Wnt Proteins Drosophila melanogaster Phenotype medicine.anatomical_structure biology.protein Signal transduction Microtubule-Associated Proteins Drosophila Protein Nuclear localization sequence Signal Transduction Transcription Factors Developmental Biology |
Zdroj: | Development. 137:e1-e1 |
ISSN: | 1477-9129 0950-1991 |
Popis: | Wg/Wnt signals specify cell fates in both invertebrate and vertebrate embryos and maintain stem-cell populations in many adult tissues. Deregulation of the Wnt pathway can transform cells to a proliferative fate, leading to cancer. We have discovered that two Drosophila proteins that are crucial for cytokinesis have a second, largely independent, role in restricting activity of the Wnt pathway. The fly homolog of RacGAP1, Tumbleweed (Tum)/RacGAP50C, and its binding partner, the kinesin-like protein Pavarotti (Pav), negatively regulate Wnt activity in fly embryos and in cultured mammalian cells. Unlike many known regulators of the Wnt pathway, these molecules do not affect stabilization of Arm/β-catenin (βcat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of βcat stabilization to control target-gene transcription. Both Tum and Pav accumulate in the nuclei of interphase cells, a location that is spatially distinct from their cleavage-furrow localization during cytokinesis. We show that this nuclear localization is essential for their role in Wnt regulation. Thus, we have identified two modulators of the Wnt pathway that have shared functions in cell division, which hints at a possible link between cytokinesis and Wnt activity during tumorigenesis. |
Databáze: | OpenAIRE |
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