Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation

• Published in: Journal of cell science Vol. 123; no. 13; pp. 2179 - 2189
• Main Authors: Jones, Whitney M, Chao, Anna T, Zavortink, Michael, Saint, Robert, Bejsovec, Amy
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01.07.2010; Company of Biologists
• Subjects: Animals; Armadillo Domain Proteins - genetics; Armadillo Domain Proteins - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Body Patterning - physiology; Cell Nucleus - metabolism; Cells, Cultured; Cytokinesis - physiology; Drosophila melanogaster - cytology; Drosophila melanogaster - embryology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epistasis, Genetic; Genes, Reporter; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Humans; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Phenotype; Signal Transduction - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Two-Hybrid System Techniques; Wings, Animal - anatomy & histology; Wings, Animal - physiology; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt1 Protein - genetics; Wnt1 Protein - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.067868

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.