@article{jones_chao_zavortink_saint_bejsovec_2010, title={Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation}, volume={123}, ISSN={0021-9533 1477-9137}, url={http://dx.doi.org/10.1242/jcs.067868}, DOI={10.1242/jcs.067868}, abstractNote={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.}, number={13}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={Jones, W. M. and Chao, A. T. and Zavortink, M. and Saint, R. and Bejsovec, A.}, year={2010}, month={Jun}, pages={2179–2189} } @article{gregory_ebrahimi_milverton_jones_bejsovec_saint_2008, title={Cell Division Requires a Direct Link between Microtubule-Bound RacGAP and Anillin in the Contractile Ring}, volume={18}, ISSN={0960-9822}, url={http://dx.doi.org/10.1016/j.cub.2007.11.050}, DOI={10.1016/j.cub.2007.11.050}, abstractNote={The mitotic microtubule array plays two primary roles in cell division. It acts as a scaffold for the congression and separation of chromosomes, and it specifies and maintains the contractile-ring position. The current model for initiation of Drosophila and mammalian cytokinesis [1-5] postulates that equatorial localization of a RhoGEF (Pbl/Ect2) by a microtubule-associated motor protein complex creates a band of activated RhoA [6], which subsequently recruits contractile-ring components such as actin, myosin, and Anillin [1-3]. Equatorial microtubules are essential for continued constriction, but how they interact with the contractile apparatus is unknown. Here, we report the first direct molecular link between the microtubule spindle and the actomyosin contractile ring. We find that the spindle-associated component, RacGAP50C, which specifies the site of cleavage [1-5], interacts directly with Anillin, an actin and myosin binding protein found in the contractile ring [7-10]. Both proteins depend on this interaction for their localization. In the absence of Anillin, the spindle-associated RacGAP loses its association with the equatorial cortex, and cytokinesis fails. These results account for the long-observed dependence of cytokinesis on the continual presence of microtubules at the cortex.}, number={1}, journal={Current Biology}, publisher={Elsevier BV}, author={Gregory, Stephen L. and Ebrahimi, Saman and Milverton, Joanne and Jones, Whitney M. and Bejsovec, Amy and Saint, Robert}, year={2008}, month={Jan}, pages={25–29} } @article{chao_jones_bejsovec_2007, title={The HMG-box transcription factor SoxNeuro acts with Tcf to control Wg/Wnt signaling activity}, volume={134}, ISSN={0950-1991 1477-9129}, url={http://dx.doi.org/10.1242/dev.02796}, DOI={10.1242/dev.02796}, abstractNote={Wnt signaling specifies cell fates in many tissues during vertebrate and invertebrate embryogenesis. To understand better how Wnt signaling is regulated during development, we have performed genetic screens to isolate mutations that suppress or enhance mutations in the fly Wnt homolog, wingless (wg). We find that loss-of-function mutations in the neural determinant SoxNeuro (also known as Sox-neuro,SoxN) partially suppress wg mutant pattern defects. SoxN encodes a HMG-box-containing protein related to the vertebrate Sox1, Sox2 and Sox3 proteins, which have been implicated in patterning events in the early mouse embryo. In Drosophila, SoxN has previously been shown to specify neural progenitors in the embryonic central nervous system. Here, we show that SoxN negatively regulates Wg pathway activity in the embryonic epidermis. Loss of SoxN function hyperactivates the Wg pathway, whereas its overexpression represses pathway activity. Epistasis analysis with other components of the Wg pathway places SoxN at the level of the transcription factor Pan (also known as Lef, Tcf) in regulating target gene expression. In human cell culture assays, SoxN represses Tcf-responsive reporter expression, indicating that the fly gene product can interact with mammalian Wnt pathway components. In both flies and in human cells, SoxN repression is potentiated by adding ectopic Tcf, suggesting that SoxN interacts with the repressor form of Tcf to influence Wg/Wnt target gene transcription.}, number={5}, journal={Development}, publisher={The Company of Biologists}, author={Chao, A. T. and Jones, W. M. and Bejsovec, A.}, year={2007}, month={Jan}, pages={989–997} } @article{jones_bejsovec_2005, title={RacGap50C Negatively Regulates Wingless Pathway Activity During Drosophila Embryonic Development}, volume={169}, ISSN={0016-6731 1943-2631}, url={http://dx.doi.org/10.1534/genetics.104.039735}, DOI={10.1534/genetics.104.039735}, abstractNote={Abstract}, number={4}, journal={Genetics}, publisher={Genetics Society of America}, author={Jones, Whitney M. and Bejsovec, Amy}, year={2005}, month={Feb}, pages={2075–2086} } @article{jones_bejsovec_2003, title={Wingless Signaling: An Axin to Grind}, volume={13}, ISSN={0960-9822}, url={http://dx.doi.org/10.1016/s0960-9822(03)00407-x}, DOI={10.1016/s0960-9822(03)00407-x}, abstractNote={Negative regulation of Wingless/Wnt signaling plays an important role in embryonic patterning and is also needed for tumor suppression in adult tissues. New findings in Drosophila reveal a novel mechanism for down-regulating the activity of the Wingless/Wnt pathway.}, number={12}, journal={Current Biology}, publisher={Elsevier BV}, author={Jones, Whitney M. and Bejsovec, Amy}, year={2003}, month={Jun}, pages={R479–R481} }