Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation.
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.
Type
Journal articleSubject
AnimalsArmadillo Domain Proteins
Body Patterning
Cell Nucleus
Cells, Cultured
Cytokinesis
Drosophila Proteins
Drosophila melanogaster
Epistasis, Genetic
GTPase-Activating Proteins
Genes, Reporter
Humans
Microtubule-Associated Proteins
Phenotype
Signal Transduction
Transcription Factors
Two-Hybrid System Techniques
Wings, Animal
Wnt Proteins
Wnt1 Protein
beta Catenin
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https://hdl.handle.net/10161/4189Published Version (Please cite this version)
10.1242/jcs.067868Publication Info
Jones, Whitney M; Chao, Anna T; Zavortink, Michael; Saint, Robert; & Bejsovec, Amy (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.
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Show full item recordScholars@Duke
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/Wn

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