Genomes and Genes
Gene Symbol: slmb
Description: supernumerary limbs
Alias: BcDNA:GM02031, CG3412, Dmel\CG3412, FBXW1, MENE (3R)-B, MENE(3R)-B, SLIMB, SLMB, Slimb, Slimb/Beta-TRCP1, Slimb/beta-TRCP, Slimb/betaTrCP, Slmb, crd, ica, l(3)00295, shv, slimb, wel, supernumerary limbs, CG3412-PA, CG3412-PB, CG3412-PC, SLIMB, centrosome replication defective, icare, pingiel, shiva, slmb-PA, slmb-PB, slmb-PC, wellman
Species: fruit fly
- Chiu J, Vanselow J, Kramer A, Edery I. The phospho-occupancy of an atypical SLIMB-binding site on PERIOD that is phosphorylated by DOUBLETIME controls the pace of the clock. Genes Dev. 2008;22:1758-72 pubmed publisher..to the rapid degradation of hyperphosphorylated isoforms via a mechanism involving the F-box protein, beta-TrCP (SLIMB in Drosophila)...
- Smelkinson M, Zhou Q, Kalderon D. Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation. Dev Cell. 2007;13:481-95 pubmed..CK1 sites on Ci create an atypical extended binding site for the SCF substrate recognition component Slimb. GSK3 enhances binding primarily through a nearby region of Ci, which might contact an SCF component other than ..
- Dzhindzhev N, Yu Q, Weiskopf K, Tzolovsky G, Cunha Ferreira I, Riparbelli M, et al. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010;467:714-8 pubmed publisher..Our findings identify independent functions for Asl as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole and organization of pericentriolar material...
- Spencer E, Jiang J, Chen Z. Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP. Genes Dev. 1999;13:284-94 pubmed..Ub) ligase complex containing the F-box/WD40-repeat protein, beta-TrCP, a vertebrate homolog of Drosophila Slimb. beta-TrCP binds to IkappaBalpha only when the latter is specifically phosphorylated by an IkappaB kinase complex...
- Caussinus E, Kanca O, Affolter M. Fluorescent fusion protein knockout mediated by anti-GFP nanobody. Nat Struct Mol Biol. 2011;19:117-21 pubmed publisher..It is traceable, because the GFP tag can be used to monitor the protein knockout. In many cases, it is a ready-to-use solution, as GFP protein-trap stock collections are being generated in Drosophila melanogaster and in Danio rerio. ..
- Jia J, Zhang L, Zhang Q, Tong C, Wang B, Hou F, et al. Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing. Dev Cell. 2005;9:819-30 pubmed..CKI phosphorylation of Ci confers binding to the F-box protein Slimb/beta-TRCP, the substrate recognition component of the SCF(Slimb/beta-TRCP) ubiquitin ligase required for Ci ..
- Zhou Q, Kalderon D. Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses. Dev Cell. 2011;20:802-14 pubmed publisher..In this model, Smo acts like many transmembrane receptors associated with cytoplasmic kinases, such that pathway activation is mediated by kinase oligomerization and trans-phosphorylation. ..
- Ohlmeyer J, Kalderon D. Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Nature. 1998;396:749-53 pubmed
- Lee S, Wang J, Yu W, Lu B. Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated A? toxicity in Drosophila. Nat Commun. 2012;3:1312 pubmed publisher..phosphorylation is targeted for ubiquitination and degradation by SCF (Skp, Cullin, F-box containing complex) (Slimb), whose action is antagonized by the deubiquitinating enzyme fat facets...
- Watts R, Hoopfer E, Luo L. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron. 2003;38:871-85 pubmed..Our findings suggest that some forms of axon pruning during development may share similarities with degeneration of axons in response to injury. ..
- Dai P, Akimaru H, Ishii S. A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci. Dev Cell. 2003;4:917-28 pubmed..Thus, Debra defines the border of the Hh-responsive region in the A compartment by inducing the lysosomal degradation of Ci. ..
- Jiang J, Struhl G. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature. 1998;391:493-6 pubmed..Here we describe a new gene, slimb (for supernumerary limbs), which negatively regulates both of these signal transduction pathways...
- Kim E, Ko H, Yu W, Hardin P, Edery I. A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential for its hyperphosphorylation, transcriptional repression, and circadian clock function. Mol Cell Biol. 2007;27:5014-28 pubmed
- Noureddine M, Donaldson T, Thacker S, Duronio R. Drosophila Roc1a encodes a RING-H2 protein with a unique function in processing the Hh signal transducer Ci by the SCF E3 ubiquitin ligase. Dev Cell. 2002;2:757-70 pubmed..We show that Roc1a mutant cells fail to proliferate. Further, while the F box protein Slimb is required for Cubitus interruptus (Ci) and Armadillo/beta-catenin (Arm) proteolysis, Roc1a mutant cells ..
- Maniatis T. A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 1999;13:505-10 pubmed
- Cunha Ferreira I, Rodrigues Martins A, Bento I, Riparbelli M, Zhang W, Laue E, et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol. 2009;19:43-9 pubmed publisher..that centrosome amplification is normally inhibited by degradation of SAK/PK4 degradation, mediated by the SCF/Slimb ubiquitin ligase...
- Theodosiou N, Zhang S, Wang W, Xu T. slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development. Development. 1998;125:3411-6 pubmed..We present evidence that slimb mutant clones in the disc deregulate wg and dpp expression in the D/V axis...
- Huangfu D, Anderson K. Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development. 2006;133:3-14 pubmed..These include intra-flagellar transport proteins, which link vertebrate Hh signaling to cilia. Because abnormal Hh signaling can cause birth defects and cancer, these vertebrate-specific components may have roles in human health. ..
- Smelkinson M, Kalderon D. Processing of the Drosophila hedgehog signaling effector Ci-155 to the repressor Ci-75 is mediated by direct binding to the SCF component Slimb. Curr Biol. 2006;16:110-6 pubmed..protein kinase A (PKA), casein kinase 1 (CK1), and glycogen synthase kinase 3 (GSK3), as well as the activity of Slimb ...
- Morais de Sá E, Vega Rioja A, Trovisco V, St Johnston D. Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF?Slimb ubiquitin ligase. Dev Cell. 2013;26:303-14 pubmed publisher..we show that Oskar is phosphorylated by Par-1 and GSK-3/Shaggy to create a phosphodegron that recruits the SCF(-Slimb) ubiquitin ligase, which targets Short Oskar for degradation...
- Miletich I, Limbourg Bouchon B. Drosophila null slimb clones transiently deregulate Hedgehog-independent transcription of wingless in all limb discs, and induce decapentaplegic transcription linked to imaginal disc regeneration. Mech Dev. 2000;93:15-26 pubmedDrosophila Slimb (Slmb) is a F-box/WD40 protein which potentially participates in the ubiquitin proteolysis machinery. During development, Slmb is required in limb discs to repress Hedgehog (Hh) target genes, i.e...
- Muzzopappa M, Wappner P. Multiple roles of the F-box protein Slimb in Drosophila egg chamber development. Development. 2005;132:2561-71 pubmed..b>Slimb (Slmb) is a Drosophila F-Box protein that fulfills several roles in development and cell physiology...
- Wang Y, Price M. A unique protection signal in Cubitus interruptus prevents its complete proteasomal degradation. Mol Cell Biol. 2008;28:5555-68 pubmed publisher..We present a model whereby the zinc finger region and K750 together form a unique protection signal that prevents the complete degradation of Ci by the proteasome. ..
- Ou C, Lin Y, Chen Y, Chien C. Distinct protein degradation mechanisms mediated by Cul1 and Cul3 controlling Ci stability in Drosophila eye development. Genes Dev. 2002;16:2403-14 pubmed..to the MF, Ci proteolytic processing promoted by PKA requires the activity of the Nedd8-modified Cul1-based SCF(Slimb) complex...
- Leulier F, Marchal C, Miletich I, Limbourg Bouchon B, Benarous R, Lemaitre B. Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses. EMBO Rep. 2003;4:976-81 pubmed
- Grima B, Lamouroux A, Chélot E, Papin C, Limbourg Bouchon B, Rouyer F. The F-box protein slimb controls the levels of clock proteins period and timeless. Nature. 2002;420:178-82 pubmed..Here we show that the product of the slimb (slmb) gene--a member of the F-box/WD40 protein family of the ubiquitin ligase SCF complex that targets ..
- Wang G, Wang B, Jiang J. Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus. Genes Dev. 1999;13:2828-37 pubmed..The proteolytic processing of Ci is promoted by the activities of protein kinase A (PKA) and Slimb, whereas it is inhibited by Hh...
- Kim S, Kim H, Kim S, Yim J. Drosophila Cand1 regulates Cullin3-dependent E3 ligases by affecting the neddylation of Cullin3 and by controlling the stability of Cullin3 and adaptor protein. Dev Biol. 2010;346:247-57 pubmed publisher..Cand1 regulates Cul3-mediated E3 ligase activity not only by acting on the neddylation of Cul3, but also by controlling the stability of the adaptor protein and unneddylated Cul3. ..
- Wojcik E, Glover D, Hays T. The SCF ubiquitin ligase protein slimb regulates centrosome duplication in Drosophila. Curr Biol. 2000;10:1131-4 pubmed..Here, we report that Slimb, an F-box protein that targets proteins to the SCFcomplex [14,15], plays a role in limiting centrosome replication...
- Hu L, Wang P, Zhao R, Li S, Wang F, Li C, et al. The Drosophila F-box protein Slimb controls dSmurf protein turnover to regulate the Hippo pathway. Biochem Biophys Res Commun. 2017;482:317-322 pubmed publisher..In the current study, we found that the F-box protein Slimb controls dSmurf protein level to regulate the Hippo pathway...
- Xi X, Lu L, Zhuge C, Chen X, Zhai Y, Cheng J, et al. The hypoparathyroidism-associated mutation in Drosophila Gcm compromises protein stability and glial cell formation. Sci Rep. 2017;7:39856 pubmed publisher..GcmR59L interacts with the Slimb-based SCF complex and Protein Kinase C (PKC), which possibly plays a role in its phosphorylation, hence altering ..
- Chen J, Verheyen E. Homeodomain-interacting protein kinase regulates Yorkie activity to promote tissue growth. Curr Biol. 2012;22:1582-6 pubmed publisher..Hipk phosphorylates Yki and in vivo analyses show that Hipk's regulation of Yki is kinase-dependent. To our knowledge, this is the first kinase identified to positively regulate Yki. ..
- Schöning J, Staiger D. At the pulse of time: protein interactions determine the pace of circadian clocks. FEBS Lett. 2005;579:3246-52 pubmed..Based on the model organisms Drosophila melanogaster and Arabidopsis thaliana molecular principles of circadian clocks are discussed in this review. ..
- Abdou M, Peng C, Huang J, Zyaan O, Wang S, Li S, et al. Wnt signaling cross-talks with JH signaling by suppressing Met and gce expression. PLoS ONE. 2011;6:e26772 pubmed publisher..We found that mutations in three Wnt signaling negative regulators in Drosophila, Axin (Axn), supernumerary limbs (slmb), and naked cuticle (nkd), caused precocious br expression, which could not be blocked by exogenous ..
- Salah Z, Aqeilan R. WW domain interactions regulate the Hippo tumor suppressor pathway. Cell Death Dis. 2011;2:e172 pubmed publisher..We further discuss new insights and future directions on the emerging role of such regulation. ..
- Marchal C, Vinatier G, Sanial M, Plessis A, Pret A, Limbourg Bouchon B, et al. The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling. PLoS ONE. 2012;7:e34310 pubmed publisher..Though our results demonstrate a physical interaction between Vpu and the proteasome-addressing SLIMB/?-TrCP protein, as in mammals, both SLIMB/?TrCP-dependent and -independent Vpu effects were observed in the ..
- Lin X, Wang F, Li Y, Zhai C, Wang G, Zhang X, et al. The SCF ubiquitin ligase Slimb controls Nerfin-1 turnover in Drosophila. Biochem Biophys Res Commun. 2018;495:629-633 pubmed publisher..Here we showed that the protein turnover of Nerfin-1 is regulated by Slimb, the substrate adaptor of SCFSlimb ubiquitin ligase complex...
- Moberg K, Mukherjee A, Veraksa A, Artavanis Tsakonas S, Hariharan I. The Drosophila F box protein archipelago regulates dMyc protein levels in vivo. Curr Biol. 2004;14:965-74 pubmed
- Jiang J. Degrading Ci: who is Cul-pable?. Genes Dev. 2002;16:2315-21 pubmed
- Fan J, Agyekum B, Venkatesan A, Hall D, Keightley A, Bjes E, et al. Noncanonical FK506-binding protein BDBT binds DBT to enhance its circadian function and forms foci at night. Neuron. 2013;80:984-96 pubmed publisher..We have named CG17282 BRIDE OF DOUBLETIME and established it as a mediator of DOUBLETIME's effects on PERIOD, most likely in cytosolic foci that regulate PERIOD nuclear accumulation. ..
- DasGupta R, Nybakken K, Booker M, Mathey Prevot B, Gonsalves F, Changkakoty B, et al. A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila. Genome Biol. 2007;8:R203 pubmed..Furthermore, we investigate other factors that may influence the outcome of such screens, including cell-type specificity, robustness of reporters, and assay normalization, which determine the efficacy of RNAi-knockdown of target genes. ..
- Klebba J, Galletta B, Nye J, Plevock K, Buster D, Hollingsworth N, et al. Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability. J Cell Biol. 2015;208:401-14 pubmed publisher..Asl not only targets Plk4 to centrioles but also modulates Plk4 stability and activity, explaining the ability of overexpressed Asl to drive centriole amplification. ..
- Khush R, Cornwell W, Uram J, Lemaitre B. A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade. Curr Biol. 2002;12:1728-37 pubmed..that target substrates to the 26S proteasome, and mutations affecting either the Drosophila SCF components, Slimb and dCullin1, or the proteasome also induce Diptericin expression...
- Bienz M. APC: the plot thickens. Curr Opin Genet Dev. 1999;9:595-603 pubmed..Recent experiments have shaped our understanding of how Axin and GSK3 function but the role of APC in this process remains elusive. ..
- Zhang Y, Wang X, Matakatsu H, Fehon R, Blair S. The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in Drosophila by binding and regulating Dachs. elife. 2016;5: pubmed publisher..Dlish tethers Dachs to the subapical cell cortex, an effect partly mediated by the palmitoyltransferase Approximated under the control of Fat. Conversely, Dlish promotes the Fat-mediated degradation of Dachs. ..
- Ogden S, Ascano M, Stegman M, Robbins D. Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol. 2004;67:805-14 pubmed..Here, we review what is known about regulation of individual Hh signaling components, concentrating on the mechanisms by which the Hh signal is propagated through Smo to the HSC. ..
- Aza Blanc P, Kornberg T. Ci: a complex transducer of the hedgehog signal. Trends Genet. 1999;15:458-62 pubmed..Here, we highlight recent advances in the Ci story, and discuss remaining questions whose resolution promise to help explain how morphogens like Hh signal their distant targets. ..
- Urban E, Nagarkar Jaiswal S, Lehner C, Heidmann S. The cohesin subunit Rad21 is required for synaptonemal complex maintenance, but not sister chromatid cohesion, during Drosophila female meiosis. PLoS Genet. 2014;10:e1004540 pubmed publisher..Thus, chromatid cohesion during female meiosis does not depend on Rad21-containing cohesin. ..
- Khire A, Vizuet A, Davila E, Avidor Reiss T. Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila. Curr Biol. 2015;25:2956-63 pubmed publisher..the master regulator of centriole duplication Plk4 and by the ubiquitin ligase that targets Plk4 for degradation: Slimb. When Asl reduction is attenuated by Asl overexpression, plk4 mutations, Plk4 RNAi, or Slimb overexpression, Asl ..
- Fearon E, Cadigan K. Cell biology. Wnt signaling glows with RNAi. Science. 2005;308:801-3 pubmed
- Mathieu J, Sung H, Pugieux C, Soetaert J, Rorth P. A sensitized PiggyBac-based screen for regulators of border cell migration in Drosophila. Genetics. 2007;176:1579-90 pubmed..We present evidence that an excess of JNK signaling is deleterious for migration in the absence of PVR activity at least in part through Fos transcriptional activity and possibly through antagonistic effects on DIAP1. ..
- Ho M, Chen H, Chen M, Jacques C, Giangrande A, Chien C. Gcm protein degradation suppresses proliferation of glial progenitors. Proc Natl Acad Sci U S A. 2009;106:6778-83 pubmed publisher..Gcm binds to 2 F-box proteins, Supernumerary limbs (Slimb) and Archipelago (Ago), adaptors of SCF E3 ubiquitin ligases...
- Johnson R, Scott M. New players and puzzles in the Hedgehog signaling pathway. Curr Opin Genet Dev. 1998;8:450-6 pubmed..The role of Hh in carcinogenesis is underscored by the identification of mutations in several pathway components in skin and brain tumors. ..
- Kuo C, Zhu S, Younger S, Jan L, Jan Y. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron. 2006;51:283-90 pubmed..Thus, in addition to uncovering E2/E3 ubiquitinating enzymes for dendrite pruning, this study provides a mechanistic link between UPS and the apoptotic machinery in regulating neuronal process remodeling. ..
- Li S, Wang C, Sandanaraj E, Aw S, Koe C, Wong J, et al. The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth. EMBO Rep. 2014;15:165-74 pubmed publisher..the SCF(Slimb) E3 ubiquitin ligase complex, which is composed of Cul1, SkpA, Roc1a and the F-box protein Supernumerary limbs (Slimb), inhibits ectopic neuroblast formation and regulates asymmetric division of neuroblasts...
- Morais de Sá E, Mukherjee A, Lowe N, St Johnston D. Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity. Development. 2014;141:2984-92 pubmed publisher..Here we show that oocyte polarity requires Slmb, the substrate specificity subunit of the SCF E3 ubiquitin ligase that targets proteins for degradation...
- Spratford C, Kumar J. Extramacrochaetae imposes order on the Drosophila eye by refining the activity of the Hedgehog signaling gradient. Development. 2013;140:1994-2004 pubmed publisher..Secondary furrow initiation along the dorsal and ventral margins is blocked by the activity of the Wingless (Wg) pathway. We also show that Emc regulates and cooperates with Wg signaling to inhibit lateral furrow initiation. ..
- Xiao H, Wang H, Silva E, Thompson J, Guillou A, Yates J, et al. The Pallbearer E3 ligase promotes actin remodeling via RAC in efferocytosis by degrading the ribosomal protein S6. Dev Cell. 2015;32:19-30 pubmed publisher..Finding a role for RpS6 in the negative regulation of efferocytosis provides the opportunity to develop new strategies to regulate this process. ..
- Grima B, Dognon A, Lamouroux A, Chélot E, Rouyer F. CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock. PLoS Biol. 2012;10:e1001367 pubmed publisher..b>SLMB, which is part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the circadian degradation of ..
- Bajpe P, van der Knaap J, Demmers J, Bezstarosti K, Bassett A, van Beusekom H, et al. Deubiquitylating enzyme UBP64 controls cell fate through stabilization of the transcriptional repressor tramtrack. Mol Cell Biol. 2008;28:1606-15 pubmed..We conclude that the balance of TTK ubiquitylation by SINA and deubiquitylation by UBP64 constitutes a specific posttranslational switch controlling cell fate. ..
- Klebba J, Buster D, McLamarrah T, Rusan N, Rogers G. Autoinhibition and relief mechanism for Polo-like kinase 4. Proc Natl Acad Sci U S A. 2015;112:E657-66 pubmed publisher..Therefore, autoinhibition delays the multiple consequences of activation until Plk4 dimerizes. These findings reveal a complex mechanism of Plk4 regulation and activation which govern the process of centriole duplication. ..
- Li X, Overton I, Baines R, Keegan L, O Connell M. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Nucleic Acids Res. 2014;42:1139-51 pubmed publisher..GABA inhibitory signalling is impaired in human epileptic and autistic conditions, and vertebrate ADARs may have a relevant evolutionarily conserved control over neuronal excitability. ..
- Skwarek L, Windler S, de Vreede G, Rogers G, Bilder D. The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells. Development. 2014;141:2978-83 pubmed publisher..Here we identify a new mechanism involving regulated protein degradation. Strong mutations in supernumerary limbs (slmb), which encodes the substrate adaptor of an SCF-class E3 ubiquitin ligase, cause dramatic loss of ..
- Fereres S, Simón R, Busturia A. A novel dRYBP-SCF complex functions to inhibit apoptosis in Drosophila. Apoptosis. 2013;18:1500-12 pubmed publisher..Given the evolutionary conservation of the dRYBP and the SCF proteins, our results suggest that their mammalian homologs may function in balancing cell survival versus cell death during normal and pathological development. ..
- Lee J, Treisman J. The role of Wingless signaling in establishing the anteroposterior and dorsoventral axes of the eye disc. Development. 2001;128:1519-29 pubmed..However, Wingless signaling does not lead to ventral mirror expression, implying the existence of ventral repressors. ..
- Dong X, Tsuda L, Zavitz K, Lin M, Li S, Carthew R, et al. ebi regulates epidermal growth factor receptor signaling pathways in Drosophila. Genes Dev. 1999;13:954-65 pubmed..Proteins with related structures regulate protein degradation. Similarly, in the developing eye, ebi promotes EGFR-dependent down-regulation of Tramtrack88, an antagonist of neuronal development. ..