Genomes and Genes
Gene Symbol: dap
Alias: CDI4, CDKN2B, CG1772, CIB1, Cdi4, DAP, Dac, Dap, Decapo, Dmel\CG1772, E(Sev-CycE)2B, P15, cdi4, dacapo/cyclin-dependent kinase interactor 4, l(2)04454, p21, p21[dacapo], p27, p27[Dap], p27cip/kip, dacapo, CG1772-PA, Cyclin-dependent kinase interactor 4, Dacap0, Dacapo/p21, chakra, dacpao, dap-PA, decapo, p21/Dacapo
Species: fruit fly
- Meyer C, Jacobs H, Datar S, Du W, Edgar B, Lehner C. Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression. EMBO J. 2000;19:4533-42 pubmed..However, the growth of cells and of the organism is reduced in Cdk4 mutants, indicating a role of D-type cyclin-dependent protein kinases in the modulation of growth rates. ..
- Hériché J, Ang D, Bier E, O Farrell P. Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila. BMC Genet. 2003;4:9 pubmed..We have used genetic and physical interactions to identify the G1/S transcription factor E2F as an SCFSlmb target in Drosophila. These results argue that the SCFSlmb ubiquitin ligase directs E2F destruction in S phase. ..
- Lane M, Elend M, Heidmann D, Herr A, Marzodko S, Herzig A, et al. A screen for modifiers of cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2. Genetics. 2000;155:233-44 pubmed..mutations that we have identified fall into four complementation groups corresponding to the genes split ends, dacapo, dE2F1, and Cdk2(Cdc2c)...
- Horsfield J, Penton A, Secombe J, Hoffman F, Richardson H. decapentaplegic is required for arrest in G1 phase during Drosophila eye development. Development. 1998;125:5069-78 pubmed..Dpp-mediated inhibition of S phase occurs independently of the Cyclin A inhibitor Roughex and of the expression of Dacapo, a Cyclin E-Cdk2 inhibitor...
- Shibutani S, Swanhart L, Duronio R. Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis. Development. 2007;134:467-78 pubmed..The initiation of G1(17) arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor...
- 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. ..
- Higa L, Yang X, Zheng J, Banks D, Wu M, Ghosh P, et al. Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation. Cell Cycle. 2006;5:71-7 pubmed..loss of CUL4 in Drosophila cells causes G(1) cell cycle arrest and an increased protein level of the CDK inhibitor Dacapo. Coelimination of Dacapo with CUL4 abolishes the G(1) cell cycle arrest...
- Audibert A, Simon F, Gho M. Cell cycle diversity involves differential regulation of Cyclin E activity in the Drosophila bristle cell lineage. Development. 2005;132:2287-97 pubmed..Cyclin E that precedes each cell division, and the differential expression of the S-transition negative regulator, Dacapo. Thus, apart from endocycles (G/S), which occurred in two out of five terminal cells, two other cell cycles ..
- Moberg K, Bell D, Wahrer D, Haber D, Hariharan I. Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature. 2001;413:311-6 pubmed..These findings implicate archipelago in developmentally regulated degradation of Cyclin E and potentially in the pathogenesis of human cancers. ..
- 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. ..
- 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..Moreover, terminal mitoses are also restored in Cyclin A mutants by either the elimination of Fizzy-related/Cdh1 function or Cyclin E overexpression. ..
- Weiss A, Herzig A, Jacobs H, Lehner C. Continuous Cyclin E expression inhibits progression through endoreduplication cycles in Drosophila. Curr Biol. 1998;8:239-42 pubmed..Our results indicate that Cyclin E activity, which triggers DNA replication, needs to be down-regulated to allow a subsequent S phase in vivo. ..
- Sukhanova M, Deb D, Gordon G, Matakatsu M, Du W. Proneural basic helix-loop-helix proteins and epidermal growth factor receptor signaling coordinately regulate cell type specification and cdk inhibitor expression during development. Mol Cell Biol. 2007;27:2987-96 pubmed..The Drosophila cdk inhibitor Dacapo (Dap) is one of the key cell cycle regulators that exhibit dynamic expression during development and contribute to ..
- Follette P, O Farrell P. Cdks and the Drosophila cell cycle. Curr Opin Genet Dev. 1997;7:17-22 pubmed..These studies encompass many aspects of the cell cycle, from the addition of a G1 phase to the cell cycle during embryogenesis to the role of cyclin degradation in progression through anaphase. ..
- Brumby A, Richardson H. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 2003;22:5769-79 pubmed
- Delanoue R, Legent K, Godefroy N, Flagiello D, Dutriaux A, Vaudin P, et al. The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc. Cell Death Differ. 2004;11:110-22 pubmed..We investigated the role of the VG-SD dimer in proliferation and showed that vg antagonizes the effect of dacapo, the cyclin-cdk inhibitor...
- Lane M, Sauer K, Wallace K, Jan Y, Lehner C, Vaessin H. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell. 1996;87:1225-35 pubmed..We show that the dacapo gene is required to arrest the epidermal cell proliferation at the correct developmental stage during Drosophila ..
- Firth L, Baker N. Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye. Dev Cell. 2005;8:541-51 pubmed..Unusually, Cyclin E levels are not limiting for retinal cell cycles. Rbf/E2F and the Cyclin E antagonist Dacapo are important, however...
- Weng L, Zhu C, Xu J, Du W. Critical role of active repression by E2F and Rb proteins in endoreplication during Drosophila development. EMBO J. 2003;22:3865-75 pubmed..These observations point to an important role for E2F-Rb complexes in the downregulation of cyclin E during the gap phase of endocycling cells in Drosophila development. ..
- Yamaguchi M, Hirose F, Inoue Y, Shiraki M, Hayashi Y, Nishi Y, et al. Ectopic expression of human p53 inhibits entry into S phase and induces apoptosis in the Drosophila eye imaginal disc. Oncogene. 1999;18:6767-75 pubmed..The transgenic flies established in this study should be useful to identify novel targets of p53 and its positive or negative regulators in Drosophila. ..
- de Nooij J, Letendre M, Hariharan I. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell. 1996;87:1237-47 pubmedIn a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors...
- 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..that Notch signaling is required for the mitotic-to-endocycle transition, through downregulating String/Cdc25, and Dacapo/p21 and upregulating Fizzy-related/Cdh1...
- Fan Y, Lee T, Xu D, Chen Z, Lamblin A, Steller H, et al. Dual roles of Drosophila p53 in cell death and cell differentiation. Cell Death Differ. 2010;17:912-21 pubmed publisher..Intriguingly, expression of the human cell-cycle inhibitor p21 or its Drosophila homolog dacapo (dap) can suppress both Dp53-induced cell death and differentiation defects in Drosophila eyes...
- Hong A, Narbonne Reveau K, Riesgo Escovar J, Fu H, Aladjem M, Lilly M. The cyclin-dependent kinase inhibitor Dacapo promotes replication licensing during Drosophila endocycles. EMBO J. 2007;26:2071-82 pubmed..Here, we demonstrate that the p21(cip1)/p27(kip1)/p57(kip2)-like cyclin-dependent kinase inhibitor (CKI), Dacapo (Dap), promotes replication licensing during Drosophila endocycles by reinforcing low Cdk activity during the ..
- Thomas B, Zavitz K, Dong X, Lane M, Weigmann K, Finley R, et al. roughex down-regulates G2 cyclins in G1. Genes Dev. 1997;11:1289-98 pubmed..These data argue that Roughex inhibits Cyclin A accumulation in early G1 by targeting Cyclin A for destruction. In late G1, Roughex is destabilized in a Cyclin E-dependent process, releasing Cyclin A for its role in S/G2. ..
- Mandal S, Freije W, Guptan P, Banerjee U. Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system. J Cell Biol. 2010;188:473-9 pubmed publisher..This regulation does not involve activation of the p27 homologue dacapo in flies. We demonstrate that regulation of cyclin E is not at the level of transcription or translation...
- Edgar B, Orr Weaver T. Endoreplication cell cycles: more for less. Cell. 2001;105:297-306 pubmed
- 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..String; a regulator of the APC ubiquitination complex Hec/CdhFzr and an inhibitor of the CyclinE/CDK complex, Dacapo. Notch activity leads to downregulation of String and Dacapo, and activation of Fzr...
- Escudero L, Freeman M. Mechanism of G1 arrest in the Drosophila eye imaginal disc. BMC Dev Biol. 2007;7:13 pubmed..The unexpectedly complex network of regulation may reflect the importance of cells being uniformly ready to respond to the inductive signals that coordinate retinal differentiation. ..
- Ghorbani M, Vasavan B, Kraja E, Swan A. Cks85A and Skp2 interact to maintain diploidy and promote growth in Drosophila. Dev Biol. 2011;358:213-23 pubmed publisher..We also find that the critical growth promoting and diploidy maintaining functions of Cks85A and Skp2 are independent of known SCF(Skp2) substrates, p27 and Cdt1, indicating that other critical substrates remain to be identified.
- Reis T, Edgar B. Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing. Cell. 2004;117:253-64 pubmed..g., by ectopic Dacapo, dWee1, dMyc, or Rheb)...
- Buttitta L, Katzaroff A, Perez C, de la Cruz A, Edgar B. A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila. Dev Cell. 2007;12:631-43 pubmed..g., neurons), known inhibitors including the retinoblastoma homolog Rbf and the p27 homolog Dacapo contribute to parallel repression of E2F and Cyclin E/Cdk2. In other cell types, however (e.g...
- Owusu Ansah E, Yavari A, Mandal S, Banerjee U. Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat Genet. 2008;40:356-61 pubmed publisher..a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial ..
- Duman Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature. 2002;417:299-304 pubmed..The discovery of a direct connection between Hh signalling and principal cell-cycle regulators provides insight into the mechanism by which deregulated Hh signalling promotes tumour formation. ..
- Xin S, Weng L, Xu J, Du W. The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth. Development. 2002;129:1345-56 pubmed
- Calvi B, Lilly M, Spradling A. Cell cycle control of chorion gene amplification. Genes Dev. 1998;12:734-44 pubmed..Our findings suggest that chorion amplification is a model for understanding metazoan replicons and the controls that restrict replication to once per cell cycle. ..
- Bowman S, Rolland V, Betschinger J, Kinsey K, Emery G, Knoblich J. The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell. 2008;14:535-46 pubmed publisher..Our data describe a transit-amplifying lineage in the Drosophila nervous system and suggest that different vulnerabilities in intermediate cell types can affect the outcome of tumor suppressor loss in stem cell lineages. ..
- Duman Scheel M, Johnston L, Du W. Repression of dMyc expression by Wingless promotes Rbf-induced G1 arrest in the presumptive Drosophila wing margin. Proc Natl Acad Sci U S A. 2004;101:3857-62 pubmed..Although Rbf/E2f pathway components mediate the ability of dMyc to promote G(1) progression, dMyc appears to regulate growth independently of the RBF/E2f pathway. ..
- Meyer C, Kramer I, Dittrich R, Marzodko S, Emmerich J, Lehner C. Drosophila p27Dacapo expression during embryogenesis is controlled by a complex regulatory region independent of cell cycle progression. Development. 2002;129:319-28 pubmedb>dacapo encodes a CIP/KIP-type inhibitor of Cyclin E/Cdk2 complexes in Drosophila melanogaster...
- Rogers G, Rusan N, Roberts D, Peifer M, Rogers S. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol. 2009;184:225-39 pubmed publisher..Using a Plk4 Slimb-binding mutant and Slimb RNAi, we show that Slimb regulates Plk4 localization to centrioles during interphase, thus regulating centriole number and ensuring the block to centriole reduplication. ..
- Liu J, MCCONNELL K, Dixon M, Calvi B. Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex. Mol Biol Cell. 2012;23:200-12 pubmed publisher..Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. ..
- Bier E, Vaessin H, Shepherd S, Lee K, McCall K, Barbel S, et al. Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 1989;3:1273-87 pubmed..This type of screen appears to be an effective way to find new loci that may play a role in the development of the Drosophila nervous system. ..
- Venkei Z, Yamashita Y. The centrosome orientation checkpoint is germline stem cell specific and operates prior to the spindle assembly checkpoint in Drosophila testis. Development. 2015;142:62-9 pubmed publisher..This study may provide a framework for identifying and understanding similar mechanisms that might be in place in other asymmetrically dividing cell types. ..
- Bivik C, MacDonald R, Gunnar E, Mazouni K, Schweisguth F, Thor S. Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling. PLoS Genet. 2016;12:e1005984 pubmed publisher..cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2)...
- Spradling A. ORC binding, gene amplification, and the nature of metazoan replication origins. Genes Dev. 1999;13:2619-23 pubmed
- Siddall N, McLaughlin E, Marriner N, Hime G. The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity. Proc Natl Acad Sci U S A. 2006;103:8402-7 pubmed..We describe the complementary expression patterns of the murine Msi paralogues Msi1 and Msi2 during spermatogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi. ..
- 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. ..
- Li Z, Liu S, Cai Y. EGFR/MAPK signaling regulates the proliferation of Drosophila renal and nephric stem cells. J Genet Genomics. 2015;42:9-20 pubmed publisher..Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury. ..
- Price D, Jin Z, Rabinovitch S, Campbell S. Ectopic expression of the Drosophila Cdk1 inhibitory kinases, Wee1 and Myt1, interferes with the second mitotic wave and disrupts pattern formation during eye development. Genetics. 2002;161:721-31 pubmed..We also observed interactions with p53, which suggest that Wee1 and Myt1 activity can block apoptosis. ..
- Lim Y, Yamasaki Y, Tsuda L. Ebi alleviates excessive growth signaling through multiple epigenetic functions in Drosophila. Genes Cells. 2013;18:909-20 pubmed publisher..Our genetic studies suggest that the antagonistic function of ebi against the Polycomb group silencing complex plays a role in the G1/S phase transition. ..
- Sutcliffe J, Brehm A. Of flies and men; p53, a tumour suppressor. FEBS Lett. 2004;567:86-91 pubmed..In addition, studying p53 in Drosophila provides an opportunity to learn about the evolution of tumour suppressors. Here, we will discuss what is known about Drosophila p53 in relation to human p53. ..
- Iida T, Lilly M. missing oocyte encodes a highly conserved nuclear protein required for the maintenance of the meiotic cycle and oocyte identity in Drosophila. Development. 2004;131:1029-39 pubmed..Our data strongly suggest that the product of the missing oocyte gene acts in the oocyte nucleus to facilitate the execution of the unique cell cycle and developmental programs that produce the mature haploid gamete. ..
- Steinhilb M, Dias Santagata D, Fulga T, Felch D, Feany M. Tau phosphorylation sites work in concert to promote neurotoxicity in vivo. Mol Biol Cell. 2007;18:5060-8 pubmed..These findings suggest that serine-proline/threonine-proline sites cooperate to mediate neurodegeneration in vivo. ..
- Warbrick E, Heatherington W, Lane D, Glover D. PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain. Nucleic Acids Res. 1998;26:3925-32 pubmed..Two of these proteins contain the consensus PCNA-binding domain: one is the Dacapo protein, a Drosophila homologue of p21(WAF1/Cip1), and the second is the transposase encoded by the Pogo DNA ..
- Zelzer E, Shilo B. Cell fate choices in Drosophila tracheal morphogenesis. Bioessays. 2000;22:219-26 pubmed..Tracheal cell fate choices are determined by signaling cascades triggered by signals emanating from the tracheal cells, as well as by ligands produced by adjacent tissues. ..
- Hatfield S, Shcherbata H, Fischer K, Nakahara K, Carthew R, Ruohola Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435:974-8 pubmed..mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint...
- 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. ..
- Manansala M, Min S, Cleary M. The Drosophila SERTAD protein Taranis determines lineage-specific neural progenitor proliferation patterns. Dev Biol. 2013;376:150-62 pubmed publisher..Our results show that lineage-specific Tara expression is necessary for proper brain development and suggest that distinct cell cycle regulatory mechanisms exist in type I versus type II neural progenitors. ..
- Ouyang Y, Song Y, Lu B. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E. PLoS ONE. 2011;6:e28098 pubmed publisher..This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence...
- 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. ..
- Zhong J, Zhang H, Stanyon C, Tromp G, Finley R. A strategy for constructing large protein interaction maps using the yeast two-hybrid system: regulated expression arrays and two-phase mating. Genome Res. 2003;13:2691-9 pubmed..We also present a three-dimensional pooling scheme to further increase the efficiency of large-scale two-hybrid analyses. ..
- Colonques J, Ceron J, Reichert H, Tejedor F. A transient expression of Prospero promotes cell cycle exit of Drosophila postembryonic neurons through the regulation of Dacapo. PLoS ONE. 2011;6:e19342 pubmed publisher..inhibits their cell cycle progression by activating the expression of the cyclin-dependent kinase inhibitor (CKI) DACAPO. These findings imply that PROSPERO, in addition to its known role as cell fate determinant in GMCs, provides a ..
- Nicholson S, Gilbert M, Nicolay B, Frolov M, Moberg K. The archipelago tumor suppressor gene limits rb/e2f-regulated apoptosis in developing Drosophila tissues. Curr Biol. 2009;19:1503-10 pubmed publisher..These phenotypes are dependent on rbf1, de2f1, hid, and the rbf1/de2f1 regulators cyclin E and dacapo but are independent of dp53...
- Kim J, Lee S, Hwang M, Ko S, Min C, Kim Ha J. Bunched specifically regulates alpha/beta mushroom body neuronal cell proliferation during metamorphosis. Neuroscience. 2009;161:46-52 pubmed publisher..We propose that bun acts as a specific factor in regulating neuroblast mitotic activity during the development of alpha/beta neurons. ..
- 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..Conversely, S-phase entry is delayed in cells in which endogenous Rca1 is replaced by a transgene lacking the F-box. We propose that Rca1 acts as an F-box protein in an as yet uncharacterized SCF complex, which promotes S-phase entry. ..
- Dekanty A, Barrio L, Milan M. Contributions of DNA repair, cell cycle checkpoints and cell death to suppressing the DNA damage-induced tumorigenic behavior of Drosophila epithelial cells. Oncogene. 2015;34:978-85 pubmed publisher..Our results support a tumor suppressor role of apoptosis, DNA repair by HR and cell cycle arrest in G2 in simple epithelia subject to IR-induced DNA damage. ..