Ccna2

Summary

Gene Symbol: Ccna2
Description: cyclin A2
Alias: AA408589, Ccn-1, Ccn1, Ccna, CycA2, Cyca, cyclin-A2, Cyclin A2 (Cyclin A), cyclin-A
Species: mouse
Products:     Ccna2

Top Publications

  1. Sweeney C, Murphy M, Kubelka M, Ravnik S, Hawkins C, Wolgemuth D, et al. A distinct cyclin A is expressed in germ cells in the mouse. Development. 1996;122:53-64 pubmed
    ..In contrast cyclin A2, which has greatest sequence identity with human cyclin A and Xenopus cyclin A2, is expressed in all tissues ..
  2. Katsuno Y, Suzuki A, Sugimura K, Okumura K, Zineldeen D, Shimada M, et al. Cyclin A-Cdk1 regulates the origin firing program in mammalian cells. Proc Natl Acad Sci U S A. 2009;106:3184-9 pubmed publisher
    ..We demonstrate here the essential role of cyclin A2-Cdk1 in the regulation of late origin firing...
  3. Kalaszczynska I, Geng Y, Iino T, Mizuno S, Choi Y, Kondratiuk I, et al. Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. Cell. 2009;138:352-65 pubmed publisher
    ..Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type ..
  4. Arsic N, Bendris N, Peter M, Begon Pescia C, Rebouissou C, Gadea G, et al. A novel function for Cyclin A2: control of cell invasion via RhoA signaling. J Cell Biol. 2012;196:147-62 pubmed publisher
    b>Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts...
  5. Wheeler L, Lents N, Baldassare J. Cyclin A-CDK activity during G1 phase impairs MCM chromatin loading and inhibits DNA synthesis in mammalian cells. Cell Cycle. 2008;7:2179-88 pubmed
    ..b>Cyclin A-CDK2 and cyclin A-CDK1 phosphorylate nuclear substrates during S and G(2) phases, respectfully...
  6. Panic L, Tamarut S, Sticker Jantscheff M, Barkic M, Solter D, Uzelac M, et al. Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Mol Cell Biol. 2006;26:8880-91 pubmed
    ..Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program. ..
  7. Kozar K, Ciemerych M, Rebel V, Shigematsu H, Zagozdzon A, Sicinska E, et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell. 2004;118:477-91 pubmed
    ..Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion. ..
  8. Chaudhry H, Dashoush N, Tang H, Zhang L, Wang X, Wu E, et al. Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium. J Biol Chem. 2004;279:35858-66 pubmed
    ..We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when ..
  9. Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P. Cdk2 knockout mice are viable. Curr Biol. 2003;13:1775-85 pubmed
    ..b>Cyclin A2 complexes were active in primary mouse embryonic fibroblasts (MEFs), embryo extracts and in spleen extracts from ..
  10. Spruck C, Strohmaier H, Watson M, Smith A, Ryan A, Krek T, et al. A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. Mol Cell. 2001;7:639-50 pubmed
    ..CKS1-/- mice are abnormally small, and cells derived from them proliferate poorly, particularly under limiting mitogen conditions, possibly due to elevated levels of p27Kip1. ..

Detail Information

Publications62

  1. Sweeney C, Murphy M, Kubelka M, Ravnik S, Hawkins C, Wolgemuth D, et al. A distinct cyclin A is expressed in germ cells in the mouse. Development. 1996;122:53-64 pubmed
    ..In contrast cyclin A2, which has greatest sequence identity with human cyclin A and Xenopus cyclin A2, is expressed in all tissues ..
  2. Katsuno Y, Suzuki A, Sugimura K, Okumura K, Zineldeen D, Shimada M, et al. Cyclin A-Cdk1 regulates the origin firing program in mammalian cells. Proc Natl Acad Sci U S A. 2009;106:3184-9 pubmed publisher
    ..We demonstrate here the essential role of cyclin A2-Cdk1 in the regulation of late origin firing...
  3. Kalaszczynska I, Geng Y, Iino T, Mizuno S, Choi Y, Kondratiuk I, et al. Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. Cell. 2009;138:352-65 pubmed publisher
    ..Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type ..
  4. Arsic N, Bendris N, Peter M, Begon Pescia C, Rebouissou C, Gadea G, et al. A novel function for Cyclin A2: control of cell invasion via RhoA signaling. J Cell Biol. 2012;196:147-62 pubmed publisher
    b>Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts...
  5. Wheeler L, Lents N, Baldassare J. Cyclin A-CDK activity during G1 phase impairs MCM chromatin loading and inhibits DNA synthesis in mammalian cells. Cell Cycle. 2008;7:2179-88 pubmed
    ..b>Cyclin A-CDK2 and cyclin A-CDK1 phosphorylate nuclear substrates during S and G(2) phases, respectfully...
  6. Panic L, Tamarut S, Sticker Jantscheff M, Barkic M, Solter D, Uzelac M, et al. Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Mol Cell Biol. 2006;26:8880-91 pubmed
    ..Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program. ..
  7. Kozar K, Ciemerych M, Rebel V, Shigematsu H, Zagozdzon A, Sicinska E, et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell. 2004;118:477-91 pubmed
    ..Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion. ..
  8. Chaudhry H, Dashoush N, Tang H, Zhang L, Wang X, Wu E, et al. Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium. J Biol Chem. 2004;279:35858-66 pubmed
    ..We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when ..
  9. Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P. Cdk2 knockout mice are viable. Curr Biol. 2003;13:1775-85 pubmed
    ..b>Cyclin A2 complexes were active in primary mouse embryonic fibroblasts (MEFs), embryo extracts and in spleen extracts from ..
  10. Spruck C, Strohmaier H, Watson M, Smith A, Ryan A, Krek T, et al. A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. Mol Cell. 2001;7:639-50 pubmed
    ..CKS1-/- mice are abnormally small, and cells derived from them proliferate poorly, particularly under limiting mitogen conditions, possibly due to elevated levels of p27Kip1. ..
  11. Sunters A, Thomas D, Yeudall W, Grigoriadis A. Accelerated cell cycle progression in osteoblasts overexpressing the c-fos proto-oncogene: induction of cyclin A and enhanced CDK2 activity. J Biol Chem. 2004;279:9882-91 pubmed
    ..Ectopic c-Fos resulted in increased expression of cyclins A and E protein levels, and premature activation of cyclin A-, cyclin E-, and cyclin-dependent kinase (CDK) 2-associated kinase activities, although cyclin D levels and CDK4 ..
  12. Berg T, Didon L, Nord M. Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development. Am J Physiol Lung Cell Mol Physiol. 2006;291:L683-93 pubmed
    ..In conclusion, our results show a role for C/EBPalpha in lung development and suggest a function in the later stages of lung branching morphogenesis. ..
  13. Milewski D, Pradhan A, Wang X, Cai Y, Le T, Turpin B, et al. FoxF1 and FoxF2 transcription factors synergistically promote rhabdomyosarcoma carcinogenesis by repressing transcription of p21Cip1 CDK inhibitor. Oncogene. 2017;36:850-862 pubmed publisher
    ..Because of the robust oncogenic activity in RMS tumors, FoxF1 and FoxF2 may represent promising targets for anti-tumor therapy. ..
  14. Krupczak Hollis K, Wang X, Kalinichenko V, Gusarova G, Wang I, Dennewitz M, et al. The mouse Forkhead Box m1 transcription factor is essential for hepatoblast mitosis and development of intrahepatic bile ducts and vessels during liver morphogenesis. Dev Biol. 2004;276:74-88 pubmed
    ....
  15. Domashenko A, Latham K, Hatton K. Expression of myc-family, myc-interacting, and myc-target genes during preimplantation mouse development. Mol Reprod Dev. 1997;47:57-65 pubmed
    ..Another putative MYC target gene, cyclin A, was expressed both as a maternal mRNA and as an embryonic transcript...
  16. Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, RONAI Z. ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell. 2005;18:577-87 pubmed
    ..ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity. ..
  17. Timchenko N, Wilde M, Darlington G. C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Mol Cell Biol. 1999;19:2936-45 pubmed
    ..S-phase-specific E2F complexes containing E2F, DP, cdk2, cyclin A, and p107 are observed in the developing liver...
  18. Philips A, Huet X, Plet A, Rech J, Vie A, Blanchard J. Anchorage-dependent expression of cyclin A in primary cells requires a negative DNA regulatory element and a functional Rb. Oncogene. 1999;18:1819-25 pubmed
    Many cells, when cultured in suspension, fail to express cyclin A, a regulatory component of cell cycle kinases cdc2 and cdk2 and as a consequence, do not enter S phase...
  19. Hirai M, Arita Y, McGlade C, Lee K, Chen J, Evans S. Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation. J Clin Invest. 2017;127:569-582 pubmed publisher
    ....
  20. Pan J, Nakade K, Huang Y, Zhu Z, Masuzaki S, Hasegawa H, et al. Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2. Oncogene. 2010;29:6245-56 pubmed publisher
    ..JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA...
  21. Sasaki T, Ito Y, Xu X, Han J, Bringas P, Maeda T, et al. LEF1 is a critical epithelial survival factor during tooth morphogenesis. Dev Biol. 2005;278:130-43 pubmed
    ..Inhibition of apoptotic activity by FGF4 rescues the tooth development in the Lef1 null mutant. Our studies suggest that LEF1 is a critical survival factor for the dental epithelial cells during tooth morphogenesis. ..
  22. Gygli P, Chang J, Gokozan H, Catacutan F, Schmidt T, Kaya B, et al. Cyclin A2 promotes DNA repair in the brain during both development and aging. Aging (Albany NY). 2016;8:1540-70 pubmed publisher
    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size ..
  23. Wolgemuth D, Lele K, Jobanputra V, Salazar G. The A-type cyclins and the meiotic cell cycle in mammalian male germ cells. Int J Androl. 2004;27:192-9 pubmed
    There are two mammalian A-type cyclins, cyclin Al and A2. While cyclin A1 is limited to male germ cells, cyclin A2 is widely expressed...
  24. Costoya J, Hobbs R, Barna M, Cattoretti G, Manova K, Sukhwani M, et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet. 2004;36:653-9 pubmed
    ..These results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool. ..
  25. Perucho L, Artero Castro A, Guerrero S, Ramon Y Cajal S, Lleonart M, Wang Z. RPLP1, a crucial ribosomal protein for embryonic development of the nervous system. PLoS ONE. 2014;9:e99956 pubmed publisher
    ..cell proliferation arrest and apoptosis due to the dysregulation of key cell cycle and apoptosis regulators (cyclin A, cyclin E, p21CIP1, p27KIP1, p53)...
  26. Porse B, Pedersen T, Hasemann M, Schuster M, Kirstetter P, Luedde T, et al. The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo. Mol Cell Biol. 2006;26:1028-37 pubmed
    ..Surprisingly, control experiments performed in C/EBPalpha null fetal livers yielded similar results. ..
  27. Cheng R, Asai T, Tang H, Dashoush N, Kara R, Costa K, et al. Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure. Circ Res. 2007;100:1741-8 pubmed
    ..Here we present a novel model system in which mice constitutively expressing cyclin A2 in the myocardium elicit a regenerative response after infarction and exhibit significantly limited ventricular ..
  28. Ezhevsky S, Toyoshima H, Hunter T, Scott D. Role of cyclin A and p27 in anti-IgM induced G1 growth arrest of murine B-cell lymphomas. Mol Biol Cell. 1996;7:553-64 pubmed
    ..Using unsynchronized cells, we previously demonstrated that cyclin A-associated and Cdk2-dependent GST-pRb kinase activity were inhibited in WEHI-231 cells treated with anti-IgM...
  29. Fuchimoto D, Mizukoshi A, Schultz R, Sakai S, Aoki F. Posttranscriptional regulation of cyclin A1 and cyclin A2 during mouse oocyte meiotic maturation and preimplantation development. Biol Reprod. 2001;65:986-93 pubmed
    ..Although cyclin A1 is proposed to regulate M phase in the meiotic cell cycle, and cyclin A2 is proposed to regulate S and M phases in the mitotic cell cycle, little is known about changes in the ..
  30. Persson J, Zhang Q, Wang X, Ravnik S, Muhlrad S, Wolgemuth D. Distinct roles for the mammalian A-type cyclins during oogenesis. Reproduction. 2005;130:411-22 pubmed
    There are two A-type cyclins in higher vertebrates, cyclin A1 and A2. Targeted mutagenesis has shown that cyclin A2 is essential for early embryonic development while cyclin A1 is required only for male meiosis...
  31. He Y, Cress W. E2F-3B is a physiological target of cyclin A. J Biol Chem. 2002;277:23493-9 pubmed
    ..Among the mechanisms that modulate the activity of the E2F proteins, cyclin A has been found to be important for the down-regulation of E2F-1, -2, and -3A activity after cells have progressed ..
  32. Bailey A, Batista P, Gold R, Chen Y, de Rooij D, Chang H, et al. The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline. elife. 2017;6: pubmed publisher
    ..YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers...
  33. Reneker L, Overbeek P. Lens-specific expression of PDGF-A alters lens growth and development. Dev Biol. 1996;180:554-65 pubmed
    ..Higher than normal levels of cyclin A and cyclin D2 expression were also detected in transgenic lens epithelium...
  34. Aleem E, Kiyokawa H, Kaldis P. Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol. 2005;7:831-6 pubmed
    ..p27 binds to Cdc2, cyclin B1, cyclin A2, or suc1 complexes in wild-type and Cdk2(-/-) extracts. In addition, cyclin E binds to and activates Cdc2...
  35. Das E, Jana N, Bhattacharyya N. MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells. Biochem Biophys Res Commun. 2013;437:217-24 pubmed publisher
    ..We observed that expression of Cyclin A2 (CCNA2), a putative target of miR-124 was increased in mutant STHdh(Q111)/Hdh(Q111) cells and brains of R6/2 ..
  36. Sekiya S, Suzuki A. Glycogen synthase kinase 3 β-dependent Snail degradation directs hepatocyte proliferation in normal liver regeneration. Proc Natl Acad Sci U S A. 2011;108:11175-80 pubmed publisher
    ..Thus, GSK-3β-dependent Snail degradation acts as a fundamental cue for the initiation of hepatocyte proliferation in liver regeneration. ..
  37. Cicero S, Herrup K. Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J Neurosci. 2005;25:9658-68 pubmed
    ..These data indicate that Cdk5 is necessary for both neuronal differentiation and cell cycle inhibition. ..
  38. Li V, Ballabeni A, Kirschner M. Gap 1 phase length and mouse embryonic stem cell self-renewal. Proc Natl Acad Sci U S A. 2012;109:12550-5 pubmed publisher
    ..The resistance of murine ESCs to differentiation induced by lengthening G1 and/or the cell cycle could allow for separate control of these events and provide new opportunities for investigation and application. ..
  39. Pacal M, Bremner R. Mapping differentiation kinetics in the mouse retina reveals an extensive period of cell cycle protein expression in post-mitotic newborn neurons. Dev Dyn. 2012;241:1525-44 pubmed publisher
    ..The high-resolution map of cell birth kinetics reported here provides a framework to better define mechanisms that regulate neurogenesis. ..
  40. Gold D, Baek S, Schork N, Rose D, Larsen D, Sachs B, et al. RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways. Neuron. 2003;40:1119-31 pubmed
    ....
  41. Chen Q, Hung F, Fromm L, Overbeek P. Induction of cell cycle entry and cell death in postmitotic lens fiber cells by overexpression of E2F1 or E2F2. Invest Ophthalmol Vis Sci. 2000;41:4223-31 pubmed
    ..Expression of either E2F1 or E2F2 can induce postmitotic lens fiber cells to re-enter the cell cycle. Inappropriate cell cycle entry is recognized by p53 in each case, and programmed cell death ensues. ..
  42. Chung H, Kim H, Jang K, Kim M, Yang J, Kang K, et al. Comprehensive analysis of differential gene expression profiles on D-galactosamine-induced acute mouse liver injury and regeneration. Toxicology. 2006;227:136-44 pubmed
    ..Furthermore, multiple genes involved in protein synthesis and degradation, mRNA processing and binding, and cell cycle regulation showed variable transcript levels upon acute GalN administration. ..
  43. Ravnik S, Wolgemuth D. The developmentally restricted pattern of expression in the male germ line of a murine cyclin A, cyclin A2, suggests roles in both mitotic and meiotic cell cycles. Dev Biol. 1996;173:69-78 pubmed
    ..b>Cyclin A2 is expressed in embryos and in a variety of adult tissues, including the testis...
  44. Sozmen M, Tunca R, Dag Erginsoy S. Cyclin A expression is associated with apoptosis and mitosis in murine 3-methylcholanthrene-induced fibrosarcomas. Exp Toxicol Pathol. 2009;61:41-9 pubmed publisher
    ..b>Cyclin A is overexpressed in various tumors, but its expression in MCA-induced fibrosarcoma in mice and its correlation to ..
  45. Hara K, Oda S, Naito K, Nagata M, Schultz R, Aoki F. Cyclin A2-CDK2 regulates embryonic gene activation in 1-cell mouse embryos. Dev Biol. 2005;286:102-13 pubmed
    ..The identity of which recruited mRNAs is responsible, however, is not known. We report here that recruitment of cyclin A2 mRNA may be critical for EGA...
  46. Liu H, Barr S, Chu C, Kohtz D, Kinoshita Y, Johnson E. Functional interaction of Puralpha with the Cdk2 moiety of cyclin A/Cdk2. Biochem Biophys Res Commun. 2005;328:851-7 pubmed
    ..Puralpha has been shown to colocalize with cyclin A/Cdk2 and to coimmunoprecipitate with cyclin A during S-phase...
  47. Singer J, Gurian West M, Clurman B, Roberts J. Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev. 1999;13:2375-87 pubmed
    ....
  48. Morice W, Wiederrecht G, Brunn G, Siekierka J, Abraham R. Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes. J Biol Chem. 1993;268:22737-45 pubmed
    ..complexes was explained, at least in part, by the association of both cyclin-dependent kinases with IL-2-induced cyclin A. RAP treatment profoundly inhibited both cyclin A expression and the appearance of active cyclin A-cyclin-..