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

Jones, Whitney M.; Chao, Anna T.; Zavortink, Michael; Saint, Robert; Bejsovec, Amy

doi:10.1242/jcs.067868

Cited by 31 publications

(23 citation statements)

References 63 publications

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“…4D,E). These observations are consistent with the idea that pbl, like tum (Jones et al, 2010), functions downstream of Arm degradation both in Drosophila cultured cells and in embryos.…”

Section: Pbl Functions Downstream Of Arm and Does Not Act Through Armsupporting

confidence: 92%

“…Indeed, some constructs lacking this region were more effective than full-length Pbl in repressing DROPflash. Second, Tum and Pav require nuclear localization to regulate Wg signaling (Jones et al, 2010). By contrast, we found no nuclear role for Pbl or ECT2 in Wg/Wnt regulation.…”

Section: Discussioncontrasting

confidence: 69%

“…Some showed pleiotropic phenotypes that had prevented them from being connected with the Wg/Wnt pathway prior to these screens. For example, the RacGTPase Activating Protein Tumbleweed (Tum) and the kinesin-like protein Pavarotti (Pav) have essential roles in cytokinesis (Somers and Saint, 2003), but also can downregulate the Wg/Wnt pathway (Jones and Bejsovec, 2005;Jones et al, 2010). In their cytokinesis role, they interact with Pebble (Pbl), a Rho guanine nucleotide exchange factor (RhoGEF), to form the centralspindlin complex.…”

Section: *Author For Correspondence (Bejsovec@dukeedu)mentioning

confidence: 99%

“…A construct that lacks this region, pbl∆N-term, localized constitutively to the cytosol, disrupting cytokinesis and mesoderm invagination (van Impel et al, 2009). Because Tum and Pav require functional NLSs to act as negative regulators of Wnt signaling (Jones et al, 2010), we investigated whether nuclear localization was important for Pbl function. Mutating the NLS (pbl∆NLS) or deleting the N-terminus (pbl∆N-term and pblDH-PH) prevented these proteins from localizing to the nucleus (van Impel et al, 2009).…”

Section: Pbl Requires Gef Domain Activity To Regulate Wg Signalingmentioning

confidence: 99%

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Pebble/ECT2 RhoGEF negatively regulates the Wingless/Wnt signaling pathway

2013

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Wingless (Wg)/Wnt signaling is essential for patterning invertebrate and vertebrate embryos, and inappropriate Wnt activity is associated with a variety of human cancers. Despite intensive study, Wnt pathway mechanisms are not fully understood. We have discovered a new mechanism for regulating the Wnt pathway: activity of a Rho guanine nucleotide exchange factor (GEF) encoded by pebble (pbl) in Drosophila and ECT2 in humans. This RhoGEF has an essential role in cytokinesis, but also plays an unexpected, conserved role in inhibiting Wg/Wnt activity. Loss and gain of pbl function in Drosophila embryos cause pattern defects that indicate altered Wg activity. Both Pbl and ECT2 repress Wg/Wnt target gene expression in cultured Drosophila and human cells. The GEF activity is required for Wnt regulation, whereas other protein domains important for cytokinesis are not. Unlike most negative regulators of Wnt activity, Pbl/ECT2 functions downstream of Armadillo (Arm)/beta-catenin stabilization. Our results indicate GTPase regulation at a novel point in Wg/Wnt signal transduction, and provide new insight into the categorization of ECT2 as a human proto-oncogene.

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“…4D,E). These observations are consistent with the idea that pbl, like tum (Jones et al, 2010), functions downstream of Arm degradation both in Drosophila cultured cells and in embryos.…”

Section: Pbl Functions Downstream Of Arm and Does Not Act Through Armsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 69%

Section: *Author For Correspondence (Bejsovec@dukeedu)mentioning

confidence: 99%

Section: Pbl Requires Gef Domain Activity To Regulate Wg Signalingmentioning

confidence: 99%

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Pebble/ECT2 RhoGEF negatively regulates the Wingless/Wnt signaling pathway

2013

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“…S4A). cdc2 and tum are genes that are required for cell cycle progression and division (Jin et al, 2005;Jones et al, 2010). l(1)10Bb and CG6066 participate in mRNA splicing (Herold et al, 2009).…”

Section: Non-cell Autonomous Effects Of Germ Cell Differentiationmentioning

confidence: 99%

Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes

Xiang

Chen

et al. 2016

Development

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The homeostasis of self-renewal and differentiation in stem cells is controlled by intrinsic signals and their niche. We conducted a large-scale RNA interference (RNAi) screen in Drosophila testes and identified 221 genes required for germline stem cell (GSC) maintenance or differentiation. Knockdown of these genes in transit-amplifying spermatogonia and cyst cells further revealed various phenotypes. Complex analysis uncovered that many of the identified genes are involved in key steps of protein synthesis and degradation. A group of genes that are required for mRNA splicing and protein translation contributes to both GSC selfrenewal and early germ cell differentiation. Loss of genes in the protein degradation pathway in cyst cells leads to testis tumors consisting of overproliferated germ cells. Importantly, in the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex, we identified multiple proteins that are crucial to GSC self-renewal: pic/DDB1, a CRL4 linker protein, is not only required for GSC self-renewal in flies but also for maintenance of spermatogonial stem cells (SSCs) in mice.

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Centralspindlin: At the heart of cytokinesis

2012

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The final step in the cell cycle is the formation of two genetically identical daughter cells by cytokinesis. At the heart of cytokinesis in animal cells is the centralspindlin complex which is comprised of two proteins, a kinesin-like protein, MKLP1, and a Rho GTPase activating protein, CYK-4. Through its targeted localization to a narrow region of antiparallel microtubule overlap immediately following chromosome segregation, centralspindlin initiates central spindle assembly. Centralspindlin has several critical functions during cell division including positioning of the division plane, regulation of Rho family GTPases, as well as midbody assembly and abscission. In this review we will examine the biochemistry of centralspindlin and its multiple functions during cell division. Remarkably, several of its critical functions are somewhat unexpected. Although endowed with motor domains, centralspindlin has an important role in generating stable, antiparallel microtubule bundles. Although it contains a Rho family GAP domain, it has a central role in the activation of RhoA during cytokinesis. Finally, centralspindlin functions as a motor protein complex, as a scaffold protein for key regulators of abscission, and as a conventional RhoGAP. Because of these diverse functions, centralspindlin lies at the heart of the cytokinetic mechanism.

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

Cited by 31 publications

References 63 publications

Pebble/ECT2 RhoGEF negatively regulates the Wingless/Wnt signaling pathway

Pebble/ECT2 RhoGEF negatively regulates the Wingless/Wnt signaling pathway

Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes

Centralspindlin: At the heart of cytokinesis

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