Abstract
We review recent advances in understanding the many cellular roles of both well-known and novel ARM-repeat proteins.
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PMID: 20688255
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Abstract
We uncover Coop (corepressor of Pan) as a Pangolin-interacting protein. Coop and Pangolin form a complex on DNA containing a Pangolin/TCF-binding motif. Overexpression of Coop specifically represses Wg target genes, while loss of Coop function causes derepression. Finally, we show that Coop antagoni...
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PMID: 20439429
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Abstract
We show here that Arm interacts with a novel BED (BEAF and Dref) finger protein that we have termed Sunspot (Ssp). Ssp transactivates Drosophila E2F-1 (dE2F-1) and PCNA expression, and positively regulates the proliferation of imaginal disc cells and the endoreplication of salivary gland cells. Wg n...
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PMID: 20430750
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Abstract
We examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remode...
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PMID: 20467587
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Abstract
We report that in prostate cancer, the methylation of CpG islands in the delta-catenin promoter was not a primary regulatory event. There was also no delta-catenin gene amplification. However, using the single-strand conformation polymorphism analysis, we observed the increased nucleotide changes in...
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PMID: 18978817
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Abstract
We employed gene transfection and small interfering RNA to demonstrate that increased delta-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. delta-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nud...
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PMID: 19284555
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Abstract
Apoptosis appears to be a carefully orchestrated process for the ordered dismantling of cells. A recent paper in BMC Developmental Biology shows that the disassembly of adherens junctions during apoptosis in Drosophila is progressive and requires the amino-terminal cleavage of the beta-catenin Armad...
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PMID: 19519938
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Abstract
We define early and late apoptotic stages and find that early in apoptosis Dalpha-catenin remains relatively stable, while Arm and DE-cadherin protein levels are strongly reduced. Arm is cleaved by caspases in embryo extracts and we provide evidence that the caspase-3 homolog drICE cleaves Arm in vi...
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PMID: 19232093
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Abstract
We identified and characterized a novel protein that interacts with pre-replication complex (pre-RC) subunits, designated Armadillo BTB Arabidopsis protein 1 (ABAP1). Overexpression of ABAP1 in plants limited mitotic DNA replication and decreased cell proliferation in leaves, whereas ABAP1 downregul...
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PMID: 18818695
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Abstract
We describe the identification of an additional APC armadillo repeat binding partner - the Striatin protein. The Striatin family members are multidomain molecules that are mainly neuronal and are thought to function as scaffolds. We have found that Striatin is expressed in epithelial cells and co-lo...
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PMID: 18502210
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Abstract
We undertake a genetic study of RanBPM function in the germline stem cell (GSC) niche of Drosophila melanogaster ovaries. We find that two RanBPM isoforms are produced from alternatively spliced transcripts, the longer of which is specifically enriched in the GSC niche, a cluster of somatic cells th...
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PMID: 18762575
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Abstract
We show that titration of xARVCF, a member of this family, to the plasma membrane disrupts adhesion in the early embryo. Adhesion can be restored by coexpression of constitutively active Rac, suggesting that intracellular signaling is the primary cause in the loss of adhesion phenotype. Our observat...
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PMID: 18729204
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Abstract
We develop an appropriate experimental approach to ascertain the existence and the physiological relevance of this phenomenon. By combining the use of magnetic tweezers with in vivo laser ablation, we locally control physiologically relevant deformations in wild-type Drosophila embryonic tissues. We...
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PMID: 18804441
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Abstract
We have identified several directly repressed targets of Wnt signalling in Drosophila. Here, we explore how individual Wnt target genes are specified for signal-induced activation or repression. Similar to activation, repression required binding of Armadillo (Arm) to the N terminus of TCF. However,...
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PMID: 18418383
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Abstract
We show that highly specific and complex protein functions can be generated by joining a low-affinity peptide-binding domain with a functionally inert second domain and subsequently optimizing the domain interface. These directed evolution processes dramatically enhanced both affinity and specificit...
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PMID: 18445649
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Abstract
We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of beta-catenin stabilization both in vivo and in cell culture. They are required for transc...
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PMID: 18451032
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Abstract
We used a yeast two-hybrid system to screen a human skeletal muscle cDNA library. alpha-Catenin was isolated as a binding protein of ARMc8alpha. This association was confirmed by co-immunoprecipitation assay using MDCK (Madin-Darby canine kidney) cells in which exogenous alpha-catenin and ARMc8alpha...
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PMID: 18215130
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Abstract
Armadillo repeat proteins are abundant eukaryotic proteins involved in several cellular processes, including signaling, transport, and cytoskeletal regulation. They are characterized by an armadillo domain, composed of tandem armadillo repeats of approximately 42 amino acids, which mediates interact...
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PMID: 18222472
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Abstract
We consider the structure, composition and function of desmosomes, and their role in embryonic development and disease....
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PMID: 17854763
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Abstract
We report the discovery of a primitive but functional SARM (CrSARM) in the immune defense of a "living fossil", the horseshoe crab, Carcinoscorpius rotundicauda. CrSARM shares numerous signature motifs and displays significant homology with vertebrate and invertebrate SARM homologues. CrSARM downreg...
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PMID: 17980913
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Abstract
We studied this process using the Wingless/Wnt pathway in Drosophila. When cells sense Wingless ligand, Armadillo (the fly beta-catenin) becomes stabilized and translocates to the nucleus, where it binds to the sequence-specific DNA binding protein TCF to activate transcription of target genes. Here...
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PMID: 18160704
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Abstract
We find that, in the Drosophila melanogaster early embryo, reduced levels of the protein kinase Akt result in incomplete centrosome migration around cortical nuclei, bent mitotic spindles, and loss of nuclei into the interior of the embryo. We show that Akt is enriched at the embryonic cortex and is...
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PMID: 18268102
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Abstract
We demonstrate that Spenito (Nito), the only other fly protein containing RRMs and a SPOC domain, acts together with Spen to positively regulate Wg signaling. The partial defect in Wg signaling observed with spen RNAi was enhanced by simultaneous knockdown of nito while it was rescued by expression...
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PMID: 18174108
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Abstract
We introduce a novel transgenic Drosophila model system for studying the effects of the major viral regulatory genes, the immediate-early genes, on normal embryonic development. We show that ectopic expression of the immediate-early genes in Drosophila led to increased embryonic lethality manifested...
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PMID: 17912601
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Abstract
We demonstrate that Drosophila Apc homologs also have an activating role in both physiological and ectopic Wingless signaling. The Apc amino terminus is important for its activating function, whereas the beta-catenin binding sites are dispensable. Apc likely promotes Wingless transduction through do...
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PMID: 18202290
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Abstract
We show that beta-catenin is a component of interphase centrosomes and that stabilization of beta-catenin, mimicking mutations found in cancers, induces centrosome splitting. Centrosomes are held together by a dynamic linker regulated by Nek2 kinase and its substrates C-Nap1 (centrosomal Nek2-associ...
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PMID: 18086858
PDF is available here.
Tatsuya T Sakai,
Hannie van der H Honing,
Miki M Nishioka,
Yukiko Y Uehara,
Mihoko M Takahashi,
Noriko N Fujisawa,
Kensuke K Saji,
Motoaki M Seki,
Kazuo K Shinozaki,
Mark A MA Jones,
Nicholas N Smirnoff,
Kiyotaka K Okada and
Geoffrey O GO Wasteneys
Abstract
We demonstrate that an armadillo repeat-containing kinesin-related protein, ARMADILLO REPEAT KINESIN1 (ARK1), is involved in root-hair morphogenesis. Microtubule polymers are more abundant in ark1 null allele root hairs, but analysis shows that these extra microtubules are concentrated in the endopl...
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PMID: 17971038
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Abstract
We provide evidence that fly Nkd acts cell-autonomously in the embryo, with its N-terminus able to confer unique functional properties and membrane association that cannot be mimicked in vivo by heterologous myristoylation consensus sequences. In conjunction with our recent observation that Nkd requ...
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PMID: 17942091
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Abstract
We have investigated membrane components in retinal extracts that interact with retinoschisin. Unlike the discoidin domain-containing blood coagulation proteins Factor V and Factor VIII, retinoschisin did not bind to phospholipids or retinal lipids reconstituted into unilamellar vesicles or immobili...
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PMID: 17804407
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Abstract
We have developed an algorithm, which we refer to as PePSSI, for flexible structural prediction of peptide binding to MHC molecules. Here, we have applied this algorithm to identify peptide epitopes (of nine amino acids, the common length) from the sequence of the cancer-testis antigen KU-CT-1, base...
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PMID: 17493854
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Abstract
We have analyzed the contribution of junctional organization of these epithelia to dorsal closure. We observe a stringent requirement for adherens junctions at the leading edge, the interface between the amnioserosa and the epidermis, for the transmission of the forces generated during the process....
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PMID: 17878238
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Abstract
We present the functional characterization of E3-ubiquitin ligase encoded by cul4B. RNAi-mediated knock-down of Cul4B in a mouse cell line C3H T10 (1/2) results in an increase in beta-catenin levels. Loss-of-function mutation in Drosophila cul4 also shows increased beta-catenin/Armadillo levels in d...
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PMID: 17954973
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Abstract
We show that epithelial polarity in the Drosophila embryo requires the exocyst complex subunit homolog Exo84. Exo84 activity is essential for the apical localization of the Crumbs transmembrane protein, a key determinant of epithelial apical identity. Adherens junction proteins become mislocalized a...
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PMID: 17698923
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Abstract
We show that the cadherin-associated protein neural plakophilin-related arm protein (NPRAP; also called delta-catenin) binds via a postsynaptic density-95 (PSD-95)/discs large/zona occludens-1 (PDZ) interaction to AMPA receptor (AMPAR)-binding protein (ABP) and the related glutamate receptor (GluR)-...
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PMID: 17687028
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Abstract
Signaling by two of the most important bacteria-sensing TLRs, TLR2 and TLR4, involves two adaptor proteins, MyD88 adaptor-like (Mal) and Toll/IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (Trif)-related adaptor molecule (TRAM). Recently, new insights into the functioning of these t...
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PMID: 17449723
PDF is available here.
Abstract
We used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components. In RanBPM, Muskelin, p48EMLP, and p44CTLH we found LisH/CTLH moti...
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PMID: 17467196
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Abstract
We address this discrepancy by demonstrating that in addition to its negative role, CBP has an essential positive role in Wnt signaling in flies. CBP binds directly to the C-terminus of Armadillo (Arm, the fly beta-cat) and is recruited to a Wnt-regulated enhancer (WRE) in a Wnt- and Arm-dependent m...
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PMID: 17410209
PDF is available here.
Abstract
Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional functions for MyD88 apart from NF-kappaB activation, including activation of the transcription factors IRF1, IRF5 and IRF7, and also a role outsi...
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PMID: 17457343
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Abstract
We find that protein phosphatase 1 (PP1), a ubiquitous serine/threonine phosphatase, is a novel potent positive physiologic regulator of the Wnt/beta-catenin signaling pathway. PP1 expression synergistically activates, and inhibition of PP1 inhibits, Wnt/beta-catenin signaling in Drosophila and mamm...
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PMID: 17318175
PDF is available here.
Abstract
We report that Pygo is associated constitutively with dTCF target genes in Drosophila salivary glands and tissue-culture cells. Our evidence indicates that this association depends on dTCF and on the Nbox motif of Pygo, but not on Legless. We thus propose an alternative model according to which Pygo...
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PMID: 17320388
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Abstract
We report that the ARM repeats of Ufd4, the E3 component of the UFD (Ub fusion degradation) pathway, recognize the Ub degradation signal of the UFD substrates. Disruption of the ARM repeats abolishes the ubiquitylating activity of Ufd4. This study uncovers a new role of the ARM repeats in protein ub...
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PMID: 17204268
PDF is available here.
Abstract
We identified a Twist target, the transmembrane protein T48, which acts in conjunction with G protein signaling to orchestrate shape changes. Together with G protein signaling, T48 recruits adherens junctions and the cytoskeletal regulator RhoGEF2 to the sites of apical constriction, ensuring rapid...
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PMID: 17234948
PDF is available here.
Abstract
Plakophilins 1-3 are members of the p120(ctn) family of armadillo-related proteins. The plakophilins have been characterized as desmosomal proteins, whereas p120(ctn) and the closely related delta-catenin, ARVCF and p0071 associate with adherens junctions and play essential roles in stabilizing cadh...
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PMID: 16765467
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Abstract
p120ctn is a member of the Armadillo protein family. It stabilizes the cadherin-catenin adhesion complex at the plasma membrane, but also has additional roles in the cytoplasm and nucleus. Extensive alternative mRNA splicing and multiple phosphorylation sites generate additional complexity. Evidence...
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PMID: 17030444
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Abstract
We examine the role of Tyrosine-142 phosphorylation in several assays and find that it is neither important for the recruitment of BCL9-2, nor for the transcriptional activity of beta-catenin in cultured mammalian cells, nor in Drosophila for Wg signaling activity in vivo. Furthermore, we demonstrat...
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PMID: 17113272
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Abstract
We show that the armadillo protein p0071, unlike its relative p120(ctn), is localized at the midbody during cytokinesis and is essential for cell division. Both knockdown and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinuc...
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PMID: 17115030
PDF is available here.
Abstract
We characterize this function of Notch in relation to Axin, a key element in the regulation of Wnt signalling that acts as a scaffold for the Shaggy/GSK3beta-dependent phosphorylation of Armadillo/beta-catenin. While Notch can regulate ectopic Wingless signalling caused by loss of function of Shaggy...
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PMID: 16881048
PDF is available here.
Abstract
We first must understand how Wnt signals are normally controlled. Naked cuticle (Nkd) is a novel and evolutionarily conserved inducible antagonist of Wnt/beta-catenin signaling that is crucial for segmentation in the model genetic organism, the fruit fly Drosophila melanogaster. Nkd can bind and inh...
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PMID: 16849595
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Abstract
We have developed an automated system based on microelectromechanical systems (MEMS) injectors for reliable mass-injection of Drosophila embryos. Targeted applications are high-throughput RNA interference (RNAi) screens. Our injection needles are made of silicon nitride. The liquid to be injected is...
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PMID: 16874371
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Abstract
We have isolated a novel splicing variant of ARMC3 from human fetal brain, which is 2439 bp, encoding a 688-amino acid polypeptide that contains three typical ARM domains. The cDNA called ARMC3_v2 and the original called ARMC3_v1 (GeneBank: BC039312) are both located on the human chromosome 10p12.23...
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PMID: 16915934
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Abstract
We show that CtBP is also required for the activation of some Wnt targets in Drosophila. CtBP is recruited to Wnt-regulated enhancers in a Wnt-dependent manner, where it augments Armadillo (the fly beta-catenin) transcriptional activation. We also found that CtBP is required for repression of a subs...
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PMID: 16710294
PDF is available here.
Abstract
We use a tissue culture system that allows conditional activation of the Wingless signaling pathway and modulation of E-cadherin expression levels. We show that activation of the Wingless signaling pathway leads to the accumulation of hypophosphorylated Armadillo in the cytoplasm and in cellular pro...
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PMID: 16720643
PDF is available here.
Abstract
We isolated six new alleles of Drosophila APC2. Two resemble the truncation alleles found in human tumors and one is a protein null. We generated ovaries and embryos null for both APC2 and APC1, and assessed the consequences of total loss of APC function, allowing us to test several previous hypothe...
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PMID: 16720878
PDF is available here.
Abstract
We verify the potential of a Drosophila model to in vivo characterize the functional consequences of HDGC-associated germline missense mutations and to identify signaling pathways affected by these mutations. To this end, we have generated transgenic fly strains expressing the wild-type hEcad gene o...
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PMID: 16600987
PDF is available here.
Abstract
We find that a constitutively active Drosophila EGFR construct does not cause any detectable changes in the level of tyrosine phosphorylation of Armadillo or destabilization of the CCC....
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PMID: 16362417
PDF is available here.
Abstract
We have used DNA microarray analyses to identify potential targets of Ultrabithorax function during haltere specification. Expression patterns of 18 validated target genes and functional analyses of a subset of these genes suggest that down-regulation of both anterior-posterior and dorso-ventral sig...
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PMID: 16414040
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Abstract
Ten years ago, par-1 and par-3 were cloned as two of the six par genes essential for the asymmetric division of the Caenorhabditis elegans zygote. PAR-1 is a protein kinase, whereas PAR-3 is a PDZ-domain-containing scaffold protein. Work over the past decade has shown that they are part of an evolut...
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PMID: 16525119
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Abstract
We demonstrate that ARABIDILLO-1 and -2 promote lateral root development. arabidillo-1/-2 mutants form fewer lateral roots, and ARABIDILLO-1-overexpressing lines produce more lateral roots than wild-type seedlings. ARABIDILLO-yellow fluorescent protein fusions are nuclear. ARABIDILLO proteins contai...
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PMID: 16434475
PDF is available here.
Abstract
We report that in the epidermis of the Drosophila embryo two signaling molecules, Hedgehog (Hh) and Wingless (Wg or Wnt1), provide directional cues that induce the proper orientation of Actin-rich structures in the larval cuticle. We further find that proper polarity in the late embryo also involves...
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PMID: 17183721
PDF is available here.