Gene Symbol: rap
Description: retina aberrant in pattern
Alias: APC/C[Fzr/Cdh1], CDH1, CG3000, Cdh1, Cdh1/Fzr, Cdh1[Fzr], Cdh[Fzr], Dmel\CG3000, Fxr, Fzr, Fzr/rap, Hec/Cdh[Fzr], Rap/Fzr, anon-WO03040301.193, cdh1, dFZR, fzr, fzr/Cdh1, l(1)G0326, l(1)G0418, rap/Fzr, rap/fizzy-related, rap/fzr, redax, wex, retina aberrant in pattern, CG3000-PA, CG3000-PB, Cdh1, Fizzy-related, Fizzy-related/Cdh1, fizzy related, fzr, rap-PA, rap-PB, redax, reduced axons, westfalenexpress
Species: fruit fly

Top Publications

  1. Acquaviva C, Pines J. The anaphase-promoting complex/cyclosome: APC/C. J Cell Sci. 2006;119:2401-4 pubmed
  2. Buttitta L, Katzaroff A, Edgar B. A robust cell cycle control mechanism limits E2F-induced proliferation of terminally differentiated cells in vivo. J Cell Biol. 2010;189:981-96 pubmed publisher
    ..These mechanisms are essential for proper development, as evading them leads to tissue outgrowths composed of dividing but terminally differentiated cells. ..
  3. Basto R, Lau J, Vinogradova T, Gardiol A, Woods C, Khodjakov A, et al. Flies without centrioles. Cell. 2006;125:1375-86 pubmed
    ..Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development. ..
  4. Grosskortenhaus R, Sprenger F. Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2. Dev Cell. 2002;2:29-40 pubmed
    ..APC activity is restricted to mitotic stages and G1 by its activators Cdc20-Fizzy (Cdc20(Fzy)) and Cdh1-Fizzy-related (Cdh1(Fzr)), respectively...
  5. Lucas E, Raff J. Maintaining the proper connection between the centrioles and the pericentriolar matrix requires Drosophila centrosomin. J Cell Biol. 2007;178:725-32 pubmed
    ..We conclude that Cnn maintains the proper connection between the centrioles and the PCM; this connection is required for accurate centriole segregation in somatic cells but is not essential for the asymmetric division of neuroblasts...
  6. Pimentel A, Venkatesh T. rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and pattern formation in the developing Drosophila eye-antennal disc. Dev Biol. 2005;285:436-46 pubmed
    The rap (retina aberrant in pattern) gene encodes the Fizzy-related protein (Fzr), which as an activator of the ubiquitin ligase complex; APC/C (anaphase promoting complex/cyclosome) facilitates the cell cycle stage-specific degradation ..
  7. Karpilow J, Kolodkin A, Bork T, Venkatesh T. Neuronal development in the Drosophila compound eye: rap gene function is required in photoreceptor cell R8 for ommatidial pattern formation. Genes Dev. 1989;3:1834-44 pubmed
    ..We describe studies on a new genetic locus rap (retina aberrant in pattern), whose functions are critical for normal pattern formation in the developing eye...
  8. Reber A, Lehner C, Jacobs H. Terminal mitoses require negative regulation of Fzr/Cdh1 by Cyclin A, preventing premature degradation of mitotic cyclins and String/Cdc25. Development. 2006;133:3201-11 pubmed
    ..Cyclin E is therefore no longer available before terminal mitoses to prevent premature Fizzy-related/Cdh1 activation...
  9. Edgar B, Orr Weaver T. Endoreplication cell cycles: more for less. Cell. 2001;105:297-306 pubmed

More Information


  1. Shibutani S, Swanhart L, Duronio R. Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis. Development. 2007;134:467-78 pubmed
    ..E2f1 protein reaccumulates in epidermal cells arrested in G1(17), and in these cells the induction of p27(Dap) activates Rbf1 to repress E2f1-target genes to maintain a stable G1 arrest. ..
  2. Sun J, Deng W. Notch-dependent downregulation of the homeodomain gene cut is required for the mitotic cycle/endocycle switch and cell differentiation in Drosophila follicle cells. Development. 2005;132:4299-308 pubmed
    ..Our data suggest that Cut functions in regulating both cell differentiation and the cell cycle, and that downregulation of Cut by Notch contributes to the mitotic cycle/endocycle switch and cell differentiation in follicle cells. ..
  3. Peel N, Stevens N, Basto R, Raff J. Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation. Curr Biol. 2007;17:834-43 pubmed
    ..Here, we investigate the effects of overexpressing the three proteins known to be required for centriole replication in Drosophila-DSas-6, DSas-4, and Sak...
  4. Narbonne Reveau K, Senger S, Pal M, Herr A, Richardson H, Asano M, et al. APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle. Development. 2008;135:1451-61 pubmed publisher
    ..In both plants and animals, the transition from the mitotic cycle to the endocycle requires Fzr/Cdh1, a positive regulator of the Anaphase-Promoting Complex/Cyclosome (APC/C)...
  5. Sigrist S, Lehner C. Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Cell. 1997;90:671-81 pubmed
    We demonstrate that fizzy-related (fzr), a conserved eukaryotic gene, negatively regulates the levels of cyclins A, B, and B3. These mitotic cyclins that bind and activate cdk1(cdc2) are rapidly degraded during exit from M and during G1...
  6. Zielke N, Querings S, Rottig C, Lehner C, Sprenger F. The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. Genes Dev. 2008;22:1690-703 pubmed publisher
    ..Geminin is only abundant in cells with high CycE-Cdk2 activity, suggesting that APC/C-Fzr activity is periodically inhibited by CycE-Cdk2, to prevent relicensing in S-phase cells.
  7. van Roessel P, Elliott D, Robinson I, Prokop A, Brand A. Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell. 2004;119:707-18 pubmed
    ..In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor. ..
  8. Raff J, Jeffers K, Huang J. The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time. J Cell Biol. 2002;157:1139-49 pubmed
    ..We show that the APC/C regulators Fizzy (Fzy)/Cdc20 and Fzy-related (Fzr)/Cdh1 bind to microtubules in vitro and associate with spindles in vivo...
  9. Jacobs H, Richter D, Venkatesh T, Lehner C. Completion of mitosis requires neither fzr/rap nor fzr2, a male germline-specific Drosophila Cdh1 homolog. Curr Biol. 2002;12:1435-41 pubmed
    Proteolysis of mitotic regulators like securins and cyclins requires Fizzy(FZY)/Cdc20 and Fizzy-related(FZR)/Hct1/Cdh1 proteins...
  10. Swan A, Schupbach T. The Cdc20 (Fzy)/Cdh1-related protein, Cort, cooperates with Fzy in cyclin destruction and anaphase progression in meiosis I and II in Drosophila. Development. 2007;134:891-9 pubmed
  11. Ruggiero R, Kale A, Thomas B, Baker N. Mitosis in neurons: Roughex and APC/C maintain cell cycle exit to prevent cytokinetic and axonal defects in Drosophila photoreceptor neurons. PLoS Genet. 2012;8:e1003049 pubmed publisher
  12. Schaeffer V, Althauser C, Shcherbata H, Deng W, Ruohola Baker H. Notch-dependent Fizzy-related/Hec1/Cdh1 expression is required for the mitotic-to-endocycle transition in Drosophila follicle cells. Curr Biol. 2004;14:630-6 pubmed
    ..By using an expression screen, we found such a component: Fizzy-related/Hec1/Cdh1 (Fzr), a WD40 repeat protein...
  13. Shcherbata H, Althauser C, Findley S, Ruohola Baker H. The mitotic-to-endocycle switch in Drosophila follicle cells is executed by Notch-dependent regulation of G1/S, G2/M and M/G1 cell-cycle transitions. Development. 2004;131:3169-81 pubmed
    ..Notch activity leads to downregulation of String and Dacapo, and activation of Fzr. All three genes are independently responsive to Notch...
  14. Jiang N, Soba P, Parker E, Kim C, Parrish J. The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth. Development. 2014;141:2657-68 pubmed publisher
    ..Hence, modulating epithelium-ECM attachment probably influences substrate permissivity for dendrite growth and contributes to the dendrite-substrate coupling that ensures proportional expansion of the two cell types. ..
  15. Schoenfelder K, Montague R, Paramore S, Lennox A, Mahowald A, Fox D. Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum. Development. 2014;141:3551-60 pubmed publisher
    ..Together, our results demonstrate that pre-mitotic endocycles can enable specific organ construction and are a mechanism that promotes highly tolerated aneuploidy. ..
  16. Harper J, Burton J, Solomon M. The anaphase-promoting complex: it's not just for mitosis any more. Genes Dev. 2002;16:2179-206 pubmed
  17. Savoian M, Rieder C. Mitosis in primary cultures of Drosophila melanogaster larval neuroblasts. J Cell Sci. 2002;115:3061-72 pubmed
  18. Meghini F, Martins T, Tait X, Fujimitsu K, Yamano H, Glover D, et al. Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit. Nat Commun. 2016;7:12607 pubmed publisher
    ..The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells...
  19. Banerjee U, Zipursky S. The role of cell-cell interaction in the development of the Drosophila visual system. Neuron. 1990;4:177-87 pubmed
  20. Basler K, Hafen E. Specification of cell fate in the developing eye of Drosophila. Bioessays. 1991;13:621-31 pubmed
    ..Genetic dissection of this pathway should therefore identify components of a signalling cascade activated by a tyrosine kinase. ..
  21. Zielke N, Kim K, Tran V, Shibutani S, Bravo M, Nagarajan S, et al. Control of Drosophila endocycles by E2F and CRL4(CDT2). Nature. 2011;480:123-7 pubmed publisher
    ..Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants, indicating that elements of this mechanism act in most growth-dependent cell cycles. ..
  22. Vidwans S, Su T. Cycling through development in Drosophila and other metazoa. Nat Cell Biol. 2001;3:E35-9 pubmed
    ..Here we present the various modes of cell-cycle regulation in metazoa and discuss their possible generation by a combination of universally conserved molecules and new regulatory circuits. ..
  23. Han Z, Bodmer R. Myogenic cells fates are antagonized by Notch only in asymmetric lineages of the Drosophila heart, with or without cell division. Development. 2003;130:3039-51 pubmed
    ..In addition, we provide evidence that whether or not Suppressor-of-Hairless can become a transcriptional activator is the key switch for the Numb/Notch activity in determining a myocardial versus pericardial cell fate. ..
  24. Irniger S. Cyclin destruction in mitosis: a crucial task of Cdc20. FEBS Lett. 2002;532:7-11 pubmed
    ..Remarkably, a complete inactivation of cyclin-dependent kinases seems to be not essential. This review discusses recent novel insights into cyclin destruction and its implications for the mitotic exit. ..
  25. Tin Su T. Cell cycle: how, when and why cells get rid of cyclin A. Curr Biol. 2001;11:R467-9 pubmed
  26. Swan A, Barcelo G, Schupbach T. Drosophila Cks30A interacts with Cdk1 to target Cyclin A for destruction in the female germline. Development. 2005;132:3669-78 pubmed
    ..We also find that a second closely related Cks gene, Cks85A, plays a distinct, non-overlapping role in Drosophila, and the two genes cannot functionally replace each other. ..
  27. Yu L, Daniels J, Glaser A, Wolf M. Raf-mediated cardiac hypertrophy in adult Drosophila. Dis Model Mech. 2013;6:964-76 pubmed publisher
    ..However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr) RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not ..
  28. Hafen E, Basler K. Specification of cell fate in the developing eye of Drosophila. Dev Suppl. 1991;1:123-30 pubmed
  29. Glover D, Hagan I, Tavares A. Polo-like kinases: a team that plays throughout mitosis. Genes Dev. 1998;12:3777-87 pubmed
  30. Djabrayan N, Cruz J, de Miguel C, Franch Marro X, Casanova J. Specification of differentiated adult progenitors via inhibition of endocycle entry in the Drosophila trachea. Cell Rep. 2014;9:859-65 pubmed publisher
    ..tracheal metamere as homologous cells from other segments, express fizzy-related (fzr), the Drosophila homolog of CDH1 protein of the APC complex, and enter endocycle and do not contribute to adult trachea...
  31. Silies M, Yuva Y, Engelen D, Aho A, Stork T, Klämbt C. Glial cell migration in the eye disc. J Neurosci. 2007;27:13130-9 pubmed
    ..Subsequent cell ablation experiments demonstrate that the carpet glia regulates glial migration in the eye disc epithelium and suggest a new model underlying glial migration and differentiation in the developing visual system. ..
  32. Franz A, Roque H, Saurya S, Dobbelaere J, Raff J. CP110 exhibits novel regulatory activities during centriole assembly in Drosophila. J Cell Biol. 2013;203:785-99 pubmed publisher
    ..Finally, and unexpectedly, CP110 suppresses centriole overduplication induced by the overexpression of centriole duplication proteins. These studies identify novel and surprising functions for CP110 in vivo in flies. ..
  33. Sato M, Kitada Y, Tabata T. Larval cells become imaginal cells under the control of homothorax prior to metamorphosis in the Drosophila tracheal system. Dev Biol. 2008;318:247-57 pubmed publisher
    ..During metamorphosis of less derived species of holometabolous insects, adult structures are known to be formed via cells constituting larval structures. Thus, the Drosophila tracheal system may utilize ancestral mode of metamorphosis. ..
  34. Mavromatakis Y, Tomlinson A. The role of the small GTPase Rap in Drosophila R7 photoreceptor specification. Proc Natl Acad Sci U S A. 2012;109:3844-9 pubmed publisher
    ..address how this high-level RTK signal is transduced in R7 and find that, in addition to Ras, another small GTPase, Rap, is also engaged...
  35. Zielke N, Querings S, Grosskortenhaus R, Reis T, Sprenger F. Molecular dissection of the APC/C inhibitor Rca1 shows a novel F-box-dependent function. EMBO Rep. 2006;7:1266-72 pubmed
    ..In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy-related (Fzr)-dependent APC/C activity...
  36. Pitsouli C, Perrimon N. Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis. Development. 2010;137:3615-24 pubmed publisher
    ..Our study establishes the series of events that lead to the formation of an adult tubular structure in Drosophila. ..
  37. Silies M, Klämbt C. APC/C(Fzr/Cdh1)-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS. Nat Neurosci. 2010;13:1357-64 pubmed publisher
    ..We found that the anaphase-promoting complex/cyclosome (APC/C) co-activator fizzy-related/Cdh1 (Fzr/Cdh1) is involved in the non-autonomous control of peripheral glial migration in postmitotic Drosophila ..
  38. Slack C, Overton P, Tuxworth R, Chia W. Asymmetric localisation of Miranda and its cargo proteins during neuroblast division requires the anaphase-promoting complex/cyclosome. Development. 2007;134:3781-7 pubmed
    ..Our results demonstrate that APC/C activity and ubiquitylation of Miranda are required for the asymmetric localisation of Miranda and its cargo proteins to the NB cortex. ..
  39. Derive N, Landmann C, Montembault E, Claverie M, Pierre Elies P, Goutte Gattat D, et al. Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes. J Cell Biol. 2015;211:517-32 pubmed publisher
    ..We therefore propose that the Bub3-BubR1 complex on broken DNA inhibits the APC/C locally via the sequestration of Cdc20, thus promoting proper transmission of broken chromosomes. ..
  40. Sun J, Deng W. Hindsight mediates the role of notch in suppressing hedgehog signaling and cell proliferation. Dev Cell. 2007;12:431-42 pubmed
    ..Our studies suggest that Hindsight bridges the two antagonistic pathways, Notch and Hedgehog, in the temporal regulation of follicle-cell proliferation and differentiation. ..
  41. Araki M, Wharton R, Tang Z, Yu H, Asano M. Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila. EMBO J. 2003;22:6115-26 pubmed
    ..These observations suggest that in Drosophila, ORC1 regulates origin utilization much as does Cdc6 in budding yeast. ..
  42. Bandura J, Jiang H, Nickerson D, Edgar B. The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster. PLoS Genet. 2013;9:e1003835 pubmed publisher
    ..Indeed, reducing the gene dosage of an inhibitor of Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell cycle exit, can genetically suppress the ..
  43. Wise A, Schatoff E, Flores J, Hua S, Ueda A, Wu C, et al. Drosophila-Cdh1 (Rap/Fzr) a regulatory subunit of APC/C is required for synaptic morphology, synaptic transmission and locomotion. Int J Dev Neurosci. 2013;31:624-33 pubmed publisher
    ..To investigate the role of APC/C-Cdh1 at the synapse we examined loss-of-function mutants of Rap/Fzr (Retina aberrant in pattern/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval ..
  44. Araki M, Yu H, Asano M. A novel motif governs APC-dependent degradation of Drosophila ORC1 in vivo. Genes Dev. 2005;19:2458-65 pubmed
    ..is degraded at the end of M phase and throughout much of G1 by anaphase-promoting complexes (APC) activated by Fzr/Cdh1. We show here that none of the previously identified APC motifs targets ORC1 for degradation...
  45. Nguyen M, Stone M, Rolls M. Microtubules are organized independently of the centrosome in Drosophila neurons. Neural Dev. 2011;6:38 pubmed publisher
    ..We conclude that the centrosome is not a major site of microtubule nucleation in Drosophila neurons, and is not required for maintenance of neuronal microtubule organization in these cells. ..
  46. Cavey M, Hijal S, Zhang X, Suter B. Drosophila valois encodes a divergent WD protein that is required for Vasa localization and Oskar protein accumulation. Development. 2005;132:459-68 pubmed
    ..Based on the structure of Vls, the function of similar proteins in different systems and our phenotypic analysis, it seems likely that vls may promote posterior patterning by facilitating interactions between different molecules. ..
  47. Pesin J, Orr Weaver T. Developmental role and regulation of cortex, a meiosis-specific anaphase-promoting complex/cyclosome activator. PLoS Genet. 2007;3:e202 pubmed
    ..Our studies reveal the mechanism for developmental regulation of an APC/C activator and suggest it is one strategy for control of the female meiotic cell cycle in a multicellular organism. ..
  48. Peters J. Subunits and substrates of the anaphase-promoting complex. Exp Cell Res. 1999;248:339-49 pubmed
    ..The APC also mediates the ubiquitin-dependent proteolysis of several other mitotic regulators, including other protein kinases, APC activators, spindle-associated proteins, and inhibitors of DNA replication. ..
  49. Jordan K, Schaeffer V, Fischer K, Gray E, Ruohola Baker H. Notch signaling through tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells. BMC Dev Biol. 2006;6:16 pubmed
    ..mitotic-to-endocycle transition, through downregulating String/Cdc25, and Dacapo/p21 and upregulating Fizzy-related/Cdh1. In this paper, we show that Notch signaling is modulated by Shaggy and temporally induced by the ligand Delta, at ..
  50. Park S, Asano M. Function of the origin recognition complex 1 (ORC1) outside DNA replication in Drosophila. Cell Cycle. 2011;10:3957-63 pubmed publisher
    ..Taken together, our results indicate the timing of ORC1 degradation is required for timely progression in M phase. ..
  51. Karpilow J, Pimentel A, Shamloula H, Venkatesh T. Neuronal development in the Drosophila compound eye: photoreceptor cells R1, R6, and R7 fail to differentiate in the retina aberrant in pattern (rap) mutant. J Neurobiol. 1996;31:149-65 pubmed
    ..Our previous work demonstrated that mutations in the retina aberrant in pattern (rap) locus lead to abnormal pattern formation in the compound eye...
  52. Kaplow M, Korayem A, Venkatesh T. Regulation of glia number in Drosophila by Rap/Fzr, an activator of the anaphase-promoting complex, and Loco, an RGS protein. Genetics. 2008;178:2003-16 pubmed publisher
    ..Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C)...
  53. Venkatesh T. Neuronal development in the Drosophila retina. J Neurobiol. 1993;24:740-56 pubmed
    ..Recent genetic and molecular studies have provided important clues regarding the nature of the molecules involved in cellular signalling and neuronal differentiation. ..
  54. Shyu L, Sun J, Chung H, Huang Y, Deng W. Notch signaling and developmental cell-cycle arrest in Drosophila polar follicle cells. Mol Biol Cell. 2009;20:5064-73 pubmed publisher
    ..Notch signaling is probably involved in down-regulating String in polar cells, thus inducing the G2 cell-cycle arrest. ..
  55. Hassel C, Zhang B, Dixon M, Calvi B. Induction of endocycles represses apoptosis independently of differentiation and predisposes cells to genome instability. Development. 2014;141:112-23 pubmed publisher
    ..However, genetic ablation of mitosis by knockdown of Cyclin A or overexpression of fzr/Cdh1 induced follicle cell endocycles and repressed apoptosis independently of Notch signaling and differentiation...
  56. Hafen E. Patterning by cell recruitment in the Drosophila eye. Curr Opin Genet Dev. 1991;1:268-74 pubmed
    ..Recent molecular genetic characterization of these interactions in Drosophila and some emerging principles of how cell fate is determined in this system are the subject of this review. ..
  57. Dobie K, Hari K, Maggert K, Karpen G. Centromere proteins and chromosome inheritance: a complex affair. Curr Opin Genet Dev. 1999;9:206-17 pubmed
    ..A picture is beginning to emerge of the centromere-kinetechore as a complex and dynamic structure with conservation of function at the protein level across diverse species. ..
  58. Qi S, Calvi B. Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in Drosophila. Mol Biol Cell. 2016;27:1885-97 pubmed publisher
    ..Our findings have important implications for understanding the coordination of cell proliferation with the apoptotic response in development and disease, including cancer and the tissue-specific responses to radiation therapy. ..