Genomes and Genes
Gene Symbol: Cdk2
Description: Cyclin-dependent kinase 2
Alias: CDC2C, CDC2c, CDK2, CDK2/CDC2c, CG10498, Cdc2c, Dcdc2c, DmCdc2c, DmCdk2, Dmcdc2c, Dmel\CG10498, S(Sev-CycE)3A, cdc2c, cdk2, dCdk2, Cyclin-dependent kinase 2, CG10498-PA, CG10498-PB, CG10498-PC, Cdk2-PA, Cdk2-PB, Cdk2-PC, cdc2c, cyclin E, cyclin-dependent kinase 2
Species: fruit fly
- Larochelle S, Pandur J, Fisher R, Salz H, Suter B. Cdk7 is essential for mitosis and for in vivo Cdk-activating kinase activity. Genes Dev. 1998;12:370-81 pubmed..These results suggest that there may be a fundamental difference in the way metazoans and budding yeast effect a key modification of Cdks. ..
- Frolov M, Stevaux O, Moon N, Dimova D, Kwon E, Morris E, et al. G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression. Genes Dev. 2003;17:723-8 pubmed..defects of dE2F1-depleted cells depend on the cooperative effects of dE2F2 and DACAPO (DAP), an inhibitor of Cyclin E/cyclin-dependent kinase 2 (CycE/cdk2)...
- 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..DNA replication in endocycling Drosophila cells is triggered by cyclin E/cyclin dependent kinase 2 (CYCE/CDK2), but this kinase must be inactivated during each G-phase to allow the assembly of pre-..
- 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..prevented or even reversed in terminally differentiating cells by the simultaneous activation of E2F1 and either Cyclin E/Cdk2 or Cyclin D/Cdk4...
- Thomer M, May N, Aggarwal B, Kwok G, Calvi B. Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2. Development. 2004;131:4807-18 pubmed..We find that phosphorylation and degradation of Dup protein at G1/S requires cyclin E/CDK2...
- 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 pubmedIn higher eukaryotes, cyclin E is thought to control the progression from G1 into S phase of the cell cycle by associating as a regulatory subunit with cdk2...
- 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..dacapo encodes an inhibitor of cyclin E/cdk2 complexes with similarity to the vertebrate Cip/Kip inhibitors...
- 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. ..
- Foley E, O Farrell P, Sprenger F. Rux is a cyclin-dependent kinase inhibitor (CKI) specific for mitotic cyclin-Cdk complexes. Curr Biol. 1999;9:1392-402 pubmed..Expression of Rux caused nuclear translocation of CycA and CycB, and inhibited Cdk1 but not Cdk2 kinase activity...
- 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..form of RBF that has four putative cdk phosphorylation sites mutated, can no longer be regulated by Cyclin D or Cyclin E. Expression of RBF-280 in the developing eye revealed that RBF-280 does not inhibit G1/S transition in the second ..
- Secombe J, Pispa J, Saint R, Richardson H. Analysis of a Drosophila cyclin E hypomorphic mutation suggests a novel role for cyclin E in cell proliferation control during eye imaginal disc development. Genetics. 1998;149:1867-82 pubmedWe have generated and characterized a Drosophila cyclin E hypomorphic mutation, DmcycEJP, that is homozygous viable and fertile, but results in adults with rough eyes...
- Faradji F, Bloyer S, Dardalhon Cuménal D, Randsholt N, Peronnet F. Drosophila melanogaster Cyclin G coordinates cell growth and cell proliferation. Cell Cycle. 2011;10:805-18 pubmed..Genetic interactions with Cyclin E suggest that Cyclin G prevents G1 to S transition and delays S phase progression...
- Tin Su T. Cell cycle: how, when and why cells get rid of cyclin A. Curr Biol. 2001;11:R467-9 pubmed
- Maurange C, Lee N, Paro R. Signaling meets chromatin during tissue regeneration in Drosophila. Curr Opin Genet Dev. 2006;16:485-9 pubmed..Understanding how signaling pathways can integrate to switch determined cells into multipotent cells has a great medical potential, especially in the field of tissue engineering and remodeling. ..
- 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. ..
- Lehner C, Lane M. Cell cycle regulators in Drosophila: downstream and part of developmental decisions. J Cell Sci. 1997;110 ( Pt 5):523-8 pubmed
- Althoff F, Viktorinova I, Kastl J, Lehner C. Drosophila Cyclin J is a mitotically stable Cdk1 partner without essential functions. Dev Biol. 2009;333:263-72 pubmed publisher..Cyclin J with EGFP fused at either N- or C-terminus binds to Cdk1 and not to Cdk2. However, in contrast to the other known Cdk1 partners, the A- and B-type cyclins, Cyclin J is not degraded during ..
- 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..In Drosophila, the activity of DmcycE/CDK2 is rate limiting for entry into S phase and we previously found that the Brm complex can suppress a reduced growth ..
- Kanao T, Sawada T, Davies S, Ichinose H, Hasegawa K, Takahashi R, et al. The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila. PLoS ONE. 2012;7:e30958 pubmed publisher..These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD. ..
- 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..gene grainyhead act combinatorially to control the precise timing of neuroblast cell-cycle exit by repressing Cyclin E and E2f...
- 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 pubmedIn addition to the previously identified Drosophila cdc2 and cdc2c genes, we have identified four additional cdc2-related genes with low stringency and polymerase chain reaction approaches...
- Barrios N, GonzÃ¡lez PÃ©rez E, HernÃ¡ndez R, Campuzano S. The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the Size of Developmental Fields. PLoS Genet. 2015;11:e1005463 pubmed publisher..Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex...
- Smith A, King J, Orr Weaver T. Identification of genomic regions required for DNA replication during Drosophila embryogenesis. Genetics. 1993;135:817-29 pubmed..Additionally, our analysis identified a gene, pimples, that is required for the proper completion of mitosis in the post-blastoderm divisions of the embryo. ..
- Stowers R, Garza D, Rascle A, Hogness D. The L63 gene is necessary for the ecdysone-induced 63E late puff and encodes CDK proteins required for Drosophila development. Dev Biol. 2000;221:23-40 pubmed..L63 proteins are widely distributed among late larval and prepupal tissues and are unlikely to be involved in cell cycle functions. ..
- 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. ..
- Farrell J, O Farrell P. From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu Rev Genet. 2014;48:269-94 pubmed publisher..Finally, we consider how the elements of this program may be conserved or changed in other organisms. ..
- Stark A, Kheradpour P, Parts L, Brennecke J, Hodges E, Hannon G, et al. Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes. Genome Res. 2007;17:1865-79 pubmed..For mir-10 in particular, both arms show abundant processing, and both show highly conserved target sites in Hox genes, suggesting a possible cooperation of the two arms, and their role as a master Hox regulator. ..
- 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. ..
- Sugaya R, Ishimaru S, Saigo K, Emori Y. Identification of a novel Drosophila gene encoding a Cdc2-related protein kinase. J Biochem. 1994;115:150-5 pubmed..Moreover, a whole mount in situ hybridization experiment showed that the Dcdrk mRNA is ubiquitously distributed in almost all embryonic cells and tissues, suggesting a universal function of Dcdrk, possibly in cell cycle regulation. ..
- Coelho C, Leevers S. Do growth and cell division rates determine cell size in multicellular organisms?. J Cell Sci. 2000;113 ( Pt 17):2927-34 pubmed..These interactions may provide a means of coordinating growth and cell division, such that cells divide only when they are above a minimum size. ..
- Clegg N, Whitehead I, Williams J, Spiegelman G, Grigliatti T. A developmental and molecular analysis of Cdc2 mutations in Drosophila melanogaster. Genome. 1993;36:676-85 pubmed..The phenotypes of our mutants are consistent with a role for Cdc2 in cell proliferation; however, we did not observe any perturbation of the endoreduplication cycle associated with the acquisition of polyteny. ..
- Farkas R, Kovacikova M, Liszeková D, Beno M, Danis P, Rabinow L, et al. Exploring some of the physico-chemical properties of the LAMMER protein kinase DOA of Drosophila. Fly (Austin). 2009;3:130-42 pubmed
- Park Y, Ng C, Datta S. Induction of string rescues the neuroblast proliferation defect in trol mutant animals. Genesis. 2003;36:187-95 pubmed..Decreasing string expression further decreased the number of S phase neuroblasts. Coexpression of cyclin E and string did not produce additional S phase cells...
- Narbonne Reveau K, Lilly M. The Cyclin-dependent kinase inhibitor Dacapo promotes genomic stability during premeiotic S phase. Mol Biol Cell. 2009;20:1960-9 pubmed publisher..In dap(-/-) females, ovarian cysts enter the meiotic cycle with high levels of Cyclin E/cyclin-dependent kinase (Cdk)2 activity and accumulate DNA damage during the premeiotic S phase...
- Lee H, Seong C, Kim Y, Davis R, Han K. Octopamine receptor OAMB is required for ovulation in Drosophila melanogaster. Dev Biol. 2003;264:179-90 pubmed..The novel expression pattern of OAMB and its genetic resource described in this study will help advance our understanding on how the neuromodulatory or endocrine system controls reproductive physiology and behavior. ..
- Rascle A, Stowers R, Garza D, Lepesant J, Hogness D. L63, the Drosophila PFTAIRE, interacts with two novel proteins unrelated to cyclins. Mech Dev. 2003;120:617-28 pubmed..Interaction between L63 and PIF-1B was confirmed in vitro and in vivo. The role of this interaction remains to be demonstrated, but our data suggest that PIF-1B might serve as a regulator of L63. ..
- Turenchalk G, St John M, Tao W, Xu T. The role of lats in cell cycle regulation and tumorigenesis. Biochim Biophys Acta. 1999;1424:M9-M16 pubmed
- Powell S, MacAlpine H, Prinz J, Li Y, Belsky J, MacAlpine D. Dynamic loading and redistribution of the Mcm2-7 helicase complex through the cell cycle. EMBO J. 2015;34:531-43 pubmed publisher..We found that in the absence of cyclin E/Cdk2 activity, there was a 10-fold decrease in chromatin-associated Mcm2-7 relative to the levels found at the G1/..
- Orr Weaver T. Developmental modification of the Drosophila cell cycle. Trends Genet. 1994;10:321-7 pubmed..The field is now poised for the identification of the intervening steps between the developmental signals and their ultimate effects on known cell cycle regulators. ..
- Remus D, Blanchette M, Rio D, Botchan M. CDK phosphorylation inhibits the DNA-binding and ATP-hydrolysis activities of the Drosophila origin recognition complex. J Biol Chem. 2005;280:39740-51 pubmed..DmORC is a substrate for both Cdk2 x cyclin E and Cdk1 x cyclin B in vitro...
- Datar S, Jacobs H, de la Cruz A, Lehner C, Edgar B. The Drosophila cyclin D-Cdk4 complex promotes cellular growth. EMBO J. 2000;19:4543-54 pubmed..Interaction tests with a Drosophila Rb homolog, RBF, indicate that CycD-Cdk4 can counteract the cell cycle suppressive effects of RBF, but that its growth promoting activity is mediated at least in part via other targets. ..
- Jacobs H, Knoblich J, Lehner C. Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B. Genes Dev. 1998;12:3741-51 pubmed..Cyclin B3 is coimmunoprecipitated with Cdk1(Cdc2) but not with Cdk2(Cdc2c). It is degraded abruptly during mitosis like Cyclins A and B...
- Wang Z, Kalderon D. Cyclin E-dependent protein kinase activity regulates niche retention of Drosophila ovarian follicle stem cells. Proc Natl Acad Sci U S A. 2009;106:21701-6 pubmed publisher..We identified a hypomorphic cyclin E allele WX that strongly impairs the maintenance of follicle stem cells (FSCs) in the Drosophila ovary but does ..
- Stern B, Ried G, Clegg N, Grigliatti T, Lehner C. Genetic analysis of the Drosophila cdc2 homolog. Development. 1993;117:219-32 pubmed..The Dm cdc2 mutant phenotype could neither be rescued with Dm cdc2c (encoding a cdc2-like kinase) nor enhanced by a reduction of the Dm cdc2c gene dose...
- Dui W, Wei B, He F, Lu W, Li C, Liang X, et al. The Drosophila F-box protein dSkp2 regulates cell proliferation by targeting Dacapo for degradation. Mol Biol Cell. 2013;24:1676-87, S1-7 pubmed publisher..Our study thus documents a conserved functional relationship between dSkp2 and Dap in their control of cell cycle progression, suggesting the possibility of using Drosophila as a model system to study Skp2-mediated tumorigenesis. ..
- Amoyel M, Simons B, Bach E. Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo. EMBO J. 2014;33:2295-313 pubmed publisher..We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process. ..
- 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..developing eye disc at the anterior edge of the morphogenetic furrow suggests that cyclin D acts early, prior to cyclin E, in inducing G1-arrested cells to enter S phase...
- Finley R, Brent R. Interaction mating reveals binary and ternary connections between Drosophila cell cycle regulators. Proc Natl Acad Sci U S A. 1994;91:12980-4 pubmed..Moreover, such analysis may also help assign function to newly identified proteins, identify domains involved in protein-protein interactions, and aid the dissection of genetic regulatory networks. ..
- Szuplewski S, Sandmann T, Hietakangas V, Cohen S. Drosophila Minus is required for cell proliferation and influences Cyclin E turnover. Genes Dev. 2009;23:1998-2003 pubmed publisher..Here we present a novel cell cycle regulator, called minus, which influences Cyclin E turnover in Drosophila...
- Zavitz K, Zipursky S. Controlling cell proliferation in differentiating tissues: genetic analysis of negative regulators of G1-->S-phase progression. Curr Opin Cell Biol. 1997;9:773-81 pubmed..Recent analysis of loss-of-function mutations in flies, worms, and mice has provided insight into the roles of various negative regulators of G1 phase in developing organisms. ..
- 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. ..
- Kolonin M, Finley R. Targeting cyclin-dependent kinases in Drosophila with peptide aptamers. Proc Natl Acad Sci U S A. 1998;95:14266-71 pubmed..each of which specifically recognizes one of the two essential cyclin-dependent kinases (Cdks), DmCdk1 and DmCdk2, in Drosophila...
- Liu J, Kipreos E. Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. Mol Biol Evol. 2000;17:1061-74 pubmed
- 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. ..
- Morris E, Michaud W, Ji J, Moon N, Rocco J, Dyson N. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet. 2006;2:e196 pubmed..Therefore, inhibition of Api5 function might offer a possible mechanism for antitumor exploitation. ..
- Rimkus S, Katzenberger R, Trinh A, Dodson G, Tibbetts R, Wassarman D. Mutations in String/CDC25 inhibit cell cycle re-entry and neurodegeneration in a Drosophila model of Ataxia telangiectasia. Genes Dev. 2008;22:1205-20 pubmed publisher..Thus, we hypothesize that ATM performs a cell cycle checkpoint function to protect post-mitotic neurons from degeneration and that cell cycle re-entry causes neurodegeneration in A-T...
- Gyuris J, Golemis E, Chertkov H, Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993;75:791-803 pubmed..In yeast, Cdi1 interacts with cyclin-dependent kinases, including human Cdc2, Cdk2, and Cdk3, but not with Ckd4...
- 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. ..
- Sukhanova M, Du W. Control of cell cycle entry and exiting from the second mitotic wave in the Drosophila developing eye. BMC Dev Biol. 2008;8:7 pubmed publisher..signaling controls S phase in the SMW by regulating Cyclin A and the E2F transcription factor independent of Cyclin E. In this manuscript, we investigate the developmental regulation of cell cycle entry into and exit from SMW...
- Lis J, Mason P, Peng J, Price D, Werner J. P-TEFb kinase recruitment and function at heat shock loci. Genes Dev. 2000;14:792-803 pubmed
- Tao W, Zhang S, Turenchalk G, Stewart R, St John M, Chen W, et al. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 1999;21:177-81 pubmed..These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a finding supported by genetic data in Drosophila demonstrating that lats specifically interacts with cdc2 and cyclin A. ..
- Lin T, Huang C, Chou W, Juang J. Abi enhances Abl-mediated CDC2 phosphorylation and inactivation. J Biomed Sci. 2004;11:902-10 pubmed..Furthermore, coexpression of Abl and Abi in Drosophila S2 cells led to suppression of cell growth. These data suggest that Abl signaling may be involved in the downregulation of Cdc2 kinase in cell cycle control. ..
- Emmerich J, Meyer C, de la Cruz A, Edgar B, Lehner C. Cyclin D does not provide essential Cdk4-independent functions in Drosophila. Genetics. 2004;168:867-75 pubmed..The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver. ..
- 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...
- Ables E, Drummond Barbosa D. Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals. Development. 2013;140:530-40 pubmed publisher..We previously observed that Cyclin E (CycE), a known G1/S regulator, is atypically expressed in GSCs during G2/M; however, it remained unclear whether ..
- 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. ..
- 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. ..
- Leclerc V, Tassan J, O Farrell P, Nigg E, Leopold P. Drosophila Cdk8, a kinase partner of cyclin C that interacts with the large subunit of RNA polymerase II. Mol Biol Cell. 1996;7:505-13 pubmed..Based on these observations and sequence similarity to the kinase/cyclin pair Srb10/Srb11 in S. cerevisiae, we suggest that cyclin C and Cdk8 control RNA polymerase II function. ..