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

Loading...
Thumbnail Image

Date

2010-07-01

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

281
views
271
downloads

Citation Stats

Abstract

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/beta-catenin (betacat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of betacat 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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1242/jcs.067868

Publication Info

Jones, Whitney M, Anna T Chao, Michael Zavortink, Robert Saint and Amy Bejsovec (2010). Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation. J Cell Sci, 123(Pt 13). pp. 2179–2189. 10.1242/jcs.067868 Retrieved from https://hdl.handle.net/10161/4189.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Bejsovec

Amy Bejsovec

Associate Professor of Biology

My laboratory explores the molecular mechanisms of pattern formation in developing embryos. We focus on the Wingless(Wg)/Wnt class of secreted growth factor: these molecules promote cell-cell communication leading to important cell fate decisions during the development of both vertebrate and invertebrate embryos. In addition, this highly conserved pathway is essential for maintaining stem cell populations and is associated with human cancers when inappropriately activated in adult tissues. Wg/Wnt molecules have proven difficult to work with biochemically because they associate tightly with cell membranes. Therefore, we exploit the powerful genetic and molecular techniques available in Drosophila to approach basic questions about Wg/Wnt signal transduction.

Current work in the lab includes analysis of genes discovered as suppressors or enhancers of wg mutant phenotypes, which may identify new control mechanisms for the pathway. In earlier work, we found that the Wg-activated transcription factor, dTCF, can act as either a repressor or an activator of Wg target genes, and our screens have uncovered other factors that may influence this genetic switch. We have also characterized a Drosophila homolog of the human tumor suppressor, APC, which negatively regulates the Wg/Wnt signaling pathway, and we are currently studying other genes that show similar properties. We use cultured human cells to determine whether gene activities we have discovered and characterized in the fly embryo are relevant to the mammalian Wnt pathway as well.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.