Genomes and Genes
Gene Symbol: CycD
Description: Cyclin D
Alias: CDI3, CG9096, CYCD, Cdi3, Cyc D, DmcycD, Dmel\CG9096, cdi3, cycD, cyclinD, dCycD, cyclin D, CG9096-PD, CG9096-PE, CG9096-PF, CycD-PD, CycD-PE, CycD-PF, Cyclin-dependent kinase interactor 3, cyclinD, dCyclinD
Species: fruit fly
- 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..This study provides a comprehensive picture of the logic that external signaling pathways may use to control cell cycle transitions by the coordinated regulation of the cell cycle. ..
- 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..Here we show that Hh signalling promotes transcription of Cyclin E and Cyclin D, two inhibitors of Rb, and principal regulators of the cell cycle during development in Drosophila...
- Baonza A, Freeman M. Control of cell proliferation in the Drosophila eye by Notch signaling. Dev Cell. 2005;8:529-39 pubmed..Delta to Notch signaling derepresses the inhibition of dE2F1 by RBF, and Delta expression depends on the secreted proteins Hedgehog and Dpp. Notch is also required for the expression of Cyclin A in the SMW. ..
- Baker N. Cell proliferation, survival, and death in the Drosophila eye. Semin Cell Dev Biol. 2001;12:499-507 pubmed..Reiterated episodes of cell death also contribute to precise regulation of retinal cell number. The EGF receptor homolog has multiple roles in retinal proliferation and survival. ..
- Sauer K, Weigmann K, Sigrist S, Lehner C. Novel members of the cdc2-related kinase family in Drosophila: cdk4/6, cdk5, PFTAIRE, and PITSLRE kinase. Mol Biol Cell. 1996;7:1759-69 pubmed..Sequence conservation and expression pattern, therefore, suggest that all of these kinases perform important cellular functions. ..
- 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. ..
- Vrailas A, Marenda D, Cook S, Powers M, Lorenzen J, Perkins L, et al. smoothened and thickveins regulate Moleskin/Importin 7-mediated MAP kinase signaling in the developing Drosophila eye. Development. 2006;133:1485-94 pubmed..Ectopic expression of Msk overcomes this block and disrupts patterning. Additionally, the MAPK cytoplasmic hold is genetically dependent on the presence of Decapentaplegic (Dpp) and Hedgehog receptors. ..
- Hétié P, de Cuevas M, Matunis E. Conversion of quiescent niche cells to somatic stem cells causes ectopic niche formation in the Drosophila testis. Cell Rep. 2014;7:715-21 pubmed publisher..Ectopic Cyclin D-Cdk4 expression in hub cells is also sufficient to trigger their conversion into CySCs...
- Das T, Dana D, Paroly S, Perumal S, Singh S, Jhun H, et al. Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis. Oncogenesis. 2013;2:e69 pubmed publisher..Our finding posits a novel role for Nek2 in promoting metastasis in addition to its currently defined role in promoting chromosomal instability. It provides a rationale for the selective advantage of centrosome amplification in cancer. ..
- Lee H, McManus C, Cho D, Eaton M, Renda F, Somma M, et al. DNA copy number evolution in Drosophila cell lines. Genome Biol. 2014;15:R70 pubmed publisher..Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis. ..
- Kugler S, Nagel A. putzig is required for cell proliferation and regulates notch activity in Drosophila. Mol Biol Cell. 2007;18:3733-40 pubmed..Our findings uncover different modes of operation of pzg during imaginal development of Drosophila, and they provide a novel mechanism of Notch regulation. ..
- 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..a mutant form of RBF that has four putative cdk phosphorylation sites mutated, can no longer be regulated by Cyclin D or Cyclin E...
- Finley R, Thomas B, Zipursky S, Brent R. Isolation of Drosophila cyclin D, a protein expressed in the morphogenetic furrow before entry into S phase. Proc Natl Acad Sci U S A. 1996;93:3011-5 pubmed..The other belongs to the D class of cyclins, previously identified in mammalian cells. We show that Drosophila cyclin D is expressed in early embryos and in imaginal disc cells in a pattern that anticipates cell divisions...
- Gupta R, Tripathi R, Naidu B, Srinivas U, Shashidhara L. Cell cycle regulation by the pro-apoptotic gene Scotin. Cell Cycle. 2008;7:2401-8 pubmed..Furthermore, a larger proportion of cells overexpressing Scotin showed sequestration of Cyclin B1 in the cytoplasm. These results suggest that one of the ways by which Scotin induces apoptosis is by causing cell cycle arrest. ..
- Zraly C, Marenda D, Dingwall A. SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex. Genetics. 2004;168:199-214 pubmed..Thus, in addition to important functions of the Brm complex in G1-S control, the complex also appears to be important for transcription of genes required for cell cycle progression. ..
- Maqbool S, Mehrotra S, Kolpakas A, Durden C, Zhang B, Zhong H, et al. Dampened activity of E2F1-DP and Myb-MuvB transcription factors in Drosophila endocycling cells. J Cell Sci. 2010;123:4095-106 pubmed publisher..Our data suggest that dampened transcriptional activation by E2F1-DP and Myb-MuvB is important to repress mitosis and coordinate the endocycle transcriptional and protein stability oscillators. ..
- Hamaratoglu F, Gajewski K, Sansores Garcia L, Morrison C, Tao C, Halder G. The Hippo tumor-suppressor pathway regulates apical-domain size in parallel to tissue growth. J Cell Sci. 2009;122:2351-9 pubmed publisher..Therefore, Hippo signaling regulates cell polarity complexes in addition to and independently of its growth control function in imaginal disc cells. ..
- Peifer M. Signal transduction. Neither straight nor narrow. Nature. 1999;400:213-5 pubmed
- Hyun J, Becam I, Yanicostas C, Bohmann D. Control of G2/M transition by Drosophila Fos. Mol Cell Biol. 2006;26:8293-302 pubmed
- Foley E, Sprenger F. Cyclins: growing pains for Drosophila. Curr Biol. 2000;10:R665-7 pubmedTradition holds that cyclin D is required for the initiation of cell division; recent studies in Drosophila, however, suggest that cyclin D has a separate function in governing growth.
- Flannery E, VanZomeren Dohm A, Beach P, Holland W, Duman Scheel M. Induction of cellular growth by the axon guidance regulators netrin A and semaphorin-1a. Dev Neurobiol. 2010;70:473-84 pubmed publisher..analyses indicated that NetA and Sema1a signaling induce expression of several growth regulators, including myc, cycD, cdk4, PCNA, and MapK in the wing disc...
- Mathe E, Kraft C, Giet R, Deak P, Peters J, Glover D. The E2-C vihar is required for the correct spatiotemporal proteolysis of cyclin B and itself undergoes cyclical degradation. Curr Biol. 2004;14:1723-33 pubmed..APC/C-mediated proteolysis of Vihar E2-C autoinactivates the APC/C at the centrosome before a second wave of proteolysis to degrade Cyclin B on the rest of the spindle and elsewhere in the cell. ..
- Nedelsky N, Pennuto M, Smith R, Palazzolo I, Moore J, Nie Z, et al. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron. 2010;67:936-52 pubmed publisher..These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases...
- 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..Our results reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition could promote genomic instability and carcinogenesis. ..
- Icreverzi A, de la Cruz A, Walker D, Edgar B. Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress. Aging Cell. 2015;14:896-906 pubmed publisher..The Drosophila Cyclin-dependent protein kinase complex cyclin D/cyclin-dependent kinase 4 (CycD/Cdk4) promotes cellular growth by stimulating mitochondrial biogenesis...
- Adlesic M, Frei C, Frew I. Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation. Biol Open. 2016;5:237-51 pubmed publisher..We show that genetic modulation of CyclinD/Cdk4 activity or mTOR-dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC ..
- Baumgardt M, Karlsson D, Salmani B, Bivik C, MacDonald R, Gunnar E, et al. Global programmed switch in neural daughter cell proliferation mode triggered by a temporal gene cascade. Dev Cell. 2014;30:192-208 pubmed publisher..This reveals a logical principle underlying progenitor and daughter cell proliferation control in the Drosophila CNS. ..
- Kim W, Jang Y, Yang J, Chung J. Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye. Dev Cell. 2017;42:363-375.e4 pubmed publisher..We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways...
- 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. ..
- Duronio R. A breath of fresh air for cyclin D/Cdk4: triggering growth via Hph. Dev Cell. 2004;6:163-4 pubmedActivation of Cyclin D/Cdk4 stimulates progression through the G1-S phase of the cell cycle in many organisms. In Drosophila, Cyclin D/Cdk4 also induces cell growth independently of cell cycle progression...
- Edgar B, Orr Weaver T. Endoreplication cell cycles: more for less. Cell. 2001;105:297-306 pubmed
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..These data suggest that intricate developmental decisions are coordinated with nutritional status and tissue growth by the InR signaling pathway. ..
- Tapon N, Moberg K, Hariharan I. The coupling of cell growth to the cell cycle. Curr Opin Cell Biol. 2001;13:731-7 pubmed..This work has revealed interesting and unexpected relationships between mechanisms that regulate growth and the cell cycle machinery. ..
- Kolonin M, Finley R. A role for cyclin J in the rapid nuclear division cycles of early Drosophila embryogenesis. Dev Biol. 2000;227:661-72 pubmed..We obtained similar results by injecting cyclin J antibodies into embryos. Our results suggest that a cyclin J-associated kinase activity is required for the early embryonic division cycles. ..
- Li L, Anderson S, Secombe J, Eisenman R. The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth. Development. 2013;140:4776-87 pubmed publisher..In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins. ..
- Chen X, Oh S, Zheng Z, Chen H, Shin H, Hou S. Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila. Dev Cell. 2003;4:179-90 pubmed..We further show that Cyclin D-Cdk4 (as well as Cyclin E-Cdk2) binds and regulates STAT92E protein stability...
- Silver D, Montell D. A new trick for Cyclin-Cdk: activation of STAT. Dev Cell. 2003;4:148-9 pubmed..Cdk4 overexpression can bypass requirements for JAK but not STAT. These results demonstrate a new function for Cdk4 and a new mode of STAT activation. ..
- Smith Bolton R, Worley M, Kanda H, Hariharan I. Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell. 2009;16:797-809 pubmed publisher..This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration. ..
- Hipfner D, Weigmann K, Cohen S. The bantam gene regulates Drosophila growth. Genetics. 2002;161:1527-37 pubmed..These effects are strikingly similar to those associated with alterations in the activity of the cyclinD-cdk4 complex...
- Rougvie A. Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues. Development. 2005;132:3787-98 pubmed..Particular attention is given to the roles of miRNAs in developmental timing and to the emerging mechanisms that link developmental programs to nutritional cues. ..
- Tseng A, Tapon N, Kanda H, Cigizoglu S, Edelmann L, Pellock B, et al. Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ras signaling pathway. Curr Biol. 2007;17:728-33 pubmed..Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs. ..
- Tang A, Neufeld T, Kwan E, Rubin G. PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism. Cell. 1997;90:459-67 pubmed
- Delanoue R, Slaidina M, Leopold P. The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Dev Cell. 2010;18:1012-21 pubmed publisher..In conclusion, the present work reveals an unexpected function of dMyc in the systemic control of growth in response to steroid hormone signaling. ..
- Debat V, Bloyer S, Faradji F, Gidaszewski N, Navarro N, Orozco Terwengel P, et al. Developmental stability: a major role for cyclin G in drosophila melanogaster. PLoS Genet. 2011;7:e1002314 pubmed publisher..We discuss the possible role of CycG as a hub in a genetic network that controls developmental stability. ..
- Khurana V, Lu Y, Steinhilb M, Oldham S, Shulman J, Feany M. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol. 2006;16:230-41 pubmed..TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model, identifying TOR and the cell cycle as potential therapeutic targets in tauopathies and AD. ..
- Nolo R, Morrison C, Tao C, Zhang X, Halder G. The bantam microRNA is a target of the hippo tumor-suppressor pathway. Curr Biol. 2006;16:1895-904 pubmed..Our data indicate that bantam is an essential target of the Hippo signaling pathway to regulate cell proliferation, cell death, and thus tissue size. ..
- Moberg K, Hariharan I. Big things from a little RNA. Trends Cell Biol. 2003;13:455-7 pubmed
- de la Cova C, Abril M, Bellosta P, Gallant P, Johnston L. Drosophila myc regulates organ size by inducing cell competition. Cell. 2004;117:107-16 pubmed..Modulating dmyc levels to create cell competition and hid-dependent cell death may be a mechanism used during normal development to control organ size. ..
- Tapon N, Ito N, Dickson B, Treisman J, Hariharan I. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001;105:345-55 pubmed..In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions. ..
- Beam C, MOBERG K. The gang of four gene regulates growth and patterning of the developing Drosophila eye. Fly (Austin). 2010;4:104-16 pubmed..Genetic reduction of bru-3 suppresses phenotypes caused by gfr alleles, and like gfr alleles, overexpression of bru-3 depresses levels of Cic protein, indicating that overexpression of bru-3 is central to gfr mutant phenotypes. ..
- Parisi F, Riccardo S, Zola S, Lora C, Grifoni D, Brown L, et al. dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1 resulting in organismal growth. Dev Biol. 2013;379:64-75 pubmed publisher..Expression of dMyc, but not of CycD/cdk4 or Rheb, in the FB diminishes the ability to retain Drosophila Insulin-like peptide-2 (DILP2) in the brain ..
- Flegel K, Sun D, Grushko O, Ma Y, Buttitta L. Live cell cycle analysis of Drosophila tissues using the Attune Acoustic Focusing Cytometer and Vybrant DyeCycle violet DNA stain. J Vis Exp. 2013;:e50239 pubmed publisher..This protocol extends the useful cell cycle analysis technique for live Drosophila tissues to a small benchtop analyzer, the Attune Acoustic Focusing Cytometer, which can be run and maintained on a single-lab scale. ..
- Shingleton A. Body-size regulation: combining genetics and physiology. Curr Biol. 2005;15:R825-7 pubmed..New research has revealed that the activity of the insulin-signaling pathway in the prothoracic gland of Drosophila modulates ecdysone release and thereby influences both the duration and rate of larval growth. ..
- Sasai N, Kato Y, Kimura G, Takeuchi T, Yamaguchi M. The Drosophila jumonji gene encodes a JmjC-containing nuclear protein that is required for metamorphosis. FEBS J. 2007;274:6139-51 pubmed..These findings suggest that dJmj controls expression of developmentally important genes through modification of chromatin into a transcriptionally silenced state. ..
- Aihara H, Nakagawa T, Mizusaki H, Yoneda M, Kato M, Doiguchi M, et al. Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1. Mol Cell. 2016;64:176-188 pubmed publisher..These results suggest that histone H2A T120 phosphorylation by hVRK1 causes inappropriate gene expression, including upregulated cyclin D1, which promotes oncogenic transformation. ..
- Layalle S, Arquier N, Leopold P. The TOR pathway couples nutrition and developmental timing in Drosophila. Dev Cell. 2008;15:568-77 pubmed publisher..In conclusion, the PG uses TOR signaling to couple nutritional input with ecdysone production and developmental timing. ..
- Gilboa L, Lehmann R. Soma-germline interactions coordinate homeostasis and growth in the Drosophila gonad. Nature. 2006;443:97-100 pubmed..We propose that similar feedback mechanisms might be generally used for coordinated growth, regeneration and homeostasis. ..
- Hafen E, Stocker H. How are the sizes of cells, organs, and bodies controlled?. PLoS Biol. 2003;1:E86 pubmed
- Malzer E, Daly M, Moloney A, Sendall T, Thomas S, Ryder E, et al. Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response. J Cell Sci. 2010;123:2892-900 pubmed publisher..PERK was both necessary and sufficient for CHK1 activation. These findings indicate that non-genotoxic misfolded protein stress accesses DNA-damage-induced cell cycle checkpoints to couple the ISR to cell cycle arrest. ..
- Gilbert M, Robinson B, Moberg K. Functional interactions between the erupted/tsg101 growth suppressor gene and the DaPKC and rbf1 genes in Drosophila imaginal disc tumors. PLoS ONE. 2009;4:e7039 pubmed publisher..Together, these data show that loss of ept alters nuclear cell cycle control in developing imaginal discs and identify the DaPKC, presenilin, and rbf1 genes as modifiers of molecular and cellular phenotypes that result from loss of ept. ..
- Vrailas A, Moses K. Smoothened, thickveins and the genetic control of cell cycle and cell fate in the developing Drosophila eye. Mech Dev. 2006;123:151-65 pubmed..We conclude that both pathways have several, but differing roles in furrow induction and cell fate and survival, but that neither directly affects cell type specification. ..
- Zhang L, Wei Y, Pushel I, Heinze K, Elenbaas J, Henry R, et al. Integrated stability and activity control of the Drosophila Rbf1 retinoblastoma protein. J Biol Chem. 2014;289:24863-73 pubmed publisher..Such functional relationships are likely to similarly impact mammalian RB family proteins, with important implications for development and disease. ..
- Baltzer C, Tiefenböck S, Marti M, Frei C. Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue through Delg and cyclin D/Cdk4. PLoS ONE. 2009;4:e6935 pubmed publisher..Our data demonstrate that Delg is critical to adjust mitochondrial abundance in respect to Cyclin D/Cdk4, a growth-promoting complex and glutamine metabolism according to nutrient availability...
- Rafel N, Milan M. Notch signalling coordinates tissue growth and wing fate specification in Drosophila. Development. 2008;135:3995-4001 pubmed publisher..These results highlight a crucial role of Notch in linking proliferation and fate specification in the developing wing primordium. ..
- Trunova S, Dubatolova T, Omel ianchuk L. [Phase-specific elements of the regulatory zone of the Drosophila melanogaster string gene]. Genetika. 2001;37:1616-20 pubmed..The regulatory regions of the stg from lines D10 and D22 and that of Drosophila gene cyclin D shared consensus aagaactttg, which was also expressed in the G1 phase...