CDK2

Summary

Gene Symbol: CDK2
Description: cyclin dependent kinase 2
Alias: CDKN2, p33(CDK2), cyclin-dependent kinase 2, cdc2-related protein kinase, cell division protein kinase 2, p33 protein kinase
Species: human
Products:     CDK2

Top Publications

  1. Stevenson L, Deal M, Hagopian J, Lew J. Activation mechanism of CDK2: role of cyclin binding versus phosphorylation. Biochemistry. 2002;41:8528-34 pubmed
    ..we describe the separate roles of cyclin A binding versus phosphorylation in the overall activation mechanism of CDK2. Interaction of CDK2 with cyclin A results in a partially active complex that is moderately defective in the ..
  2. Ortega S, Prieto I, Odajima J, Martin A, Dubus P, Sotillo R, et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet. 2003;35:25-31 pubmed
    We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells...
  3. Henneke G, Koundrioukoff S, Hubscher U. Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation. Oncogene. 2003;22:4301-13 pubmed
    ..Our results suggest a novel regulatory role of Cdks onto the end of S phase by targeting directly a key enzyme involved in DNA replication. ..
  4. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153-66 pubmed publisher
    ..Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias. ..
  5. Bockstaele L, Kooken H, Libert F, Paternot S, Dumont J, De Launoit Y, et al. Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Mol Cell Biol. 2006;26:5070-85 pubmed
    ..Collectively, these unexpected observations indicate that CDK4-activating kinase(s) should be reconsidered. ..
  6. Otyepka M, Bártová I, Kriz Z, Koca J. Different mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics. J Biol Chem. 2006;281:7271-81 pubmed
    ..In addition, the results obtained on the behavior of CDK5 are compared with data on CDK2 to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) ..
  7. Zhou Y, Ching Y, Chun A, Jin D. Nuclear localization of the cell cycle regulator CDH1 and its regulation by phosphorylation. J Biol Chem. 2003;278:12530-6 pubmed
    ..On the other hand, abolition of the cyclin-binding ability of CDH1 has no influence on its nuclear localization. Taken together, our findings document the phosphorylation-dependent localization of CDH1 in vertebrate cells. ..
  8. Nekhai S, Jeang K. Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev. Future Microbiol. 2006;1:417-26 pubmed
    ..Tat interacts with protein kinase complexes Cdk9/cyclin T1 and Cdk2/cyclin E; acetyltransferases p300/CBP, p300/CBP-associated factor and hGCN5; protein phosphatases and other factors...
  9. Lunn C, Chrivia J, Baldassare J. Activation of Cdk2/Cyclin E complexes is dependent on the origin of replication licensing factor Cdc6 in mammalian cells. Cell Cycle. 2010;9:4533-41 pubmed
    Cyclin E-associated CDK2 activity is required for the initiation of DNA synthesis in human cells...

More Information

Publications86

  1. Bártová I, Koca J, Otyepka M. Regulatory phosphorylation of cyclin-dependent kinase 2: insights from molecular dynamics simulations. J Mol Model. 2008;14:761-8 pubmed publisher
    The structures of fully active cyclin-dependent kinase-2 (CDK2) complexed with ATP and peptide substrate, CDK2 after the catalytic reaction, and CDK2 inhibited by phosphorylation at Thr14/Tyr15 were studied using molecular dynamics (MD) ..
  2. Spencer S, Cappell S, Tsai F, Overton K, Wang C, Meyer T. The proliferation-quiescence decision is controlled by a bifurcation in CDK2 activity at mitotic exit. Cell. 2013;155:369-83 pubmed publisher
    ..Here, we introduce a live-cell sensor for CDK2 activity and unexpectedly found that proliferating cells bifurcate into two populations as they exit mitosis...
  3. Chen Z, Indjeian V, McManus M, Wang L, Dynlacht B. CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. Dev Cell. 2002;3:339-50 pubmed
    ..Our data suggest that CP110 is a physiological centrosomal CDK target that promotes centrosome duplication, and its deregulation may contribute to genomic instability. ..
  4. Stevenson Lindert L, Fowler P, Lew J. Substrate specificity of CDK2-cyclin A. What is optimal?. J Biol Chem. 2003;278:50956-60 pubmed
    ..The catalytic efficiency of CDK2-cyclin A is impaired 2000-, 10-, and 150-fold, when Pro+1, Lys+2, or Lys+3, respectively, is substituted with Ala ..
  5. Afanasyeva E, Mestdagh P, Kumps C, Vandesompele J, Ehemann V, Theissen J, et al. MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ. 2011;18:974-84 pubmed publisher
    ..Enforced miR-885-5p expression consistently leads to downregulation of cyclin-dependent kinase (CDK2) and mini-chromosome maintenance protein (MCM5)...
  6. Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler W, et al. C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol Cell. 2001;8:817-28 pubmed
    ..We found that C/EBPalpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases...
  7. Muller Tidow C, Ji P, Diederichs S, Potratz J, Baumer N, Kohler G, et al. The cyclin A1-CDK2 complex regulates DNA double-strand break repair. Mol Cell Biol. 2004;24:8917-28 pubmed
    Vertebrates express two A-type cyclins; both associate with and activate the CDK2 protein kinase. Cyclin A1 is required in the male germ line, but its molecular functions are incompletely understood...
  8. Merrick K, Larochelle S, Zhang C, Allen J, Shokat K, Fisher R. Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells. Mol Cell. 2008;32:662-72 pubmed publisher
    ..these preferences in human cells and show that cyclin A assembles with Cdk1 only after complex formation with Cdk2 reaches a plateau during late S and G2 phases...
  9. Merrick K, Wohlbold L, Zhang C, Allen J, Horiuchi D, Huskey N, et al. Switching Cdk2 on or off with small molecules to reveal requirements in human cell proliferation. Mol Cell. 2011;42:624-36 pubmed publisher
    ..During the mammalian cell cycle, Cdk2 forms active complexes before Cdk1, but lack of Cdk2 protein does not block cell-cycle progression...
  10. Chow J, Siu W, Ho H, Ma K, Ho C, Poon R. Differential contribution of inhibitory phosphorylation of CDC2 and CDK2 for unperturbed cell cycle control and DNA integrity checkpoints. J Biol Chem. 2003;278:40815-28 pubmed
    ..this study, we compared the relative contribution of inhibitory phosphorylation for cyclin A/B1-CDC2 and cyclin A/E-CDK2 complexes...
  11. Huang X, Summers M, Pham V, Lill J, Liu J, Lee G, et al. Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Mol Cell. 2011;42:511-23 pubmed publisher
    ..Phosphorylation of USP37 by CDK2 stimulated its full activity...
  12. Grim J, Gustafson M, Hirata R, Hagar A, Swanger J, Welcker M, et al. Isoform- and cell cycle-dependent substrate degradation by the Fbw7 ubiquitin ligase. J Cell Biol. 2008;181:913-20 pubmed publisher
    ..to Fbw7 varies during the cell cycle, and this correlates with changes in cyclin E-cyclin-dependent kinase 2 (CDK2)-specific activity, cyclin E autophosphorylation, and CDK2 inhibitory phosphorylation...
  13. LARREA M, Hong F, Wander S, da Silva T, HELFMAN D, Lannigan D, et al. RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility. Proc Natl Acad Sci U S A. 2009;106:9268-73 pubmed publisher
  14. Bashir T, Pagan J, Busino L, Pagano M. Phosphorylation of Ser72 is dispensable for Skp2 assembly into an active SCF ubiquitin ligase and its subcellular localization. Cell Cycle. 2010;9:971-4 pubmed
  15. Coulonval K, Bockstaele L, Paternot S, Roger P. Phosphorylations of cyclin-dependent kinase 2 revisited using two-dimensional gel electrophoresis. J Biol Chem. 2003;278:52052-60 pubmed
    ..To re-assess the precise relationship between the different phosphorylations of CDK2, and the influence of cyclins and CDK inhibitors upon them, we introduce here the use of the high resolution power ..
  16. Zhu H, Nie L, Maki C. Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif. J Biol Chem. 2005;280:29282-8 pubmed
    ..Recent studies have suggested that Cdk2 activity may promote p21 degradation through a pathway similar to that for p27, although the mechanism by which ..
  17. Wolthuis R, Clay Farrace L, van Zon W, Yekezare M, Koop L, Ogink J, et al. Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A. Mol Cell. 2008;30:290-302 pubmed publisher
    ..Thus, we identify a crucial role for the Cks proteins in mitosis and one mechanism by which the APC/C can target substrates independently of the spindle checkpoint. ..
  18. Debebe Z, Ammosova T, Jerebtsova M, Kurantsin Mills J, Niu X, Charles S, et al. Iron chelators ICL670 and 311 inhibit HIV-1 transcription. Virology. 2007;367:324-33 pubmed
    ..311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2)...
  19. Gayther S, Song H, Ramus S, Kjaer S, Whittemore A, Quaye L, et al. Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer. Cancer Res. 2007;67:3027-35 pubmed
    ..approach to evaluate common variants in 13 genes involved in cell cycle control-CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D-and risk of invasive epithelial ovarian cancer...
  20. Song H, Hanlon N, Brown N, Noble M, Johnson L, Barford D. Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell. 2001;7:615-26 pubmed
    The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity...
  21. Baldassarre G, Belletti B, Nicoloso M, Schiappacassi M, Vecchione A, Spessotto P, et al. p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion. Cancer Cell. 2005;7:51-63 pubmed
    ..This study provides a functional link between proliferation and invasion of tumor cells based on diverse activities of p27(kip1) in different subcellular compartments. ..
  22. Olsen J, Vermeulen M, Santamaria A, Kumar C, Miller M, Jensen L, et al. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010;3:ra3 pubmed publisher
    ..than 5000 sites and found that most of the up-regulated sites phosphorylated by cyclin-dependent kinase 1 (CDK1) or CDK2 were almost fully phosphorylated in mitotic cells...
  23. Debebe Z, Ammosova T, Breuer D, Lovejoy D, Kalinowski D, Kumar K, et al. Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets--iron, cyclin-dependent kinase (CDK) 2, and CDK9. Mol Pharmacol. 2011;79:185-96 pubmed publisher
    ..Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl ..
  24. Tian R, Wang X, Hou L, Jia W, Yang Q, Li Y, et al. MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis. J Biol Chem. 2011;286:25556-63 pubmed publisher
    ..We used bioinformatic predictions to determine that CDK2 and cyclin A1 were possible targets of miR-372 and confirmed this prediction using a fluorescent reporter assay...
  25. Tetsu O, McCormick F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell. 2003;3:233-45 pubmed
    We have investigated the contribution of CDK4 and CDK2 inhibition to G1 arrest in colon cancers following inhibition of the MEK/MAP kinase pathway...
  26. Deng L, Ammosova T, Pumfery A, Kashanchi F, Nekhai S. HIV-1 Tat interaction with RNA polymerase II C-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter. J Biol Chem. 2002;277:33922-9 pubmed
    ..We reported a Tat-associated T-cell-derived kinase, which contained CDK2. Here, we provide further evidence that CDK2 is involved in Tat-mediated CTD phosphorylation and in HIV-1 ..
  27. Nekhai S, Zhou M, Fernandez A, Lane W, Lamb N, Brady J, et al. HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2, phosphorylates CDK7 and stimulates Tat-mediated transcription. Biochem J. 2002;364:649-57 pubmed
    ..TTK uniquely co-purified with CDK2 and not with either CDK9 or CDK7...
  28. Chen S, Bohrer L, Rai A, Pan Y, Gan L, Zhou X, et al. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol. 2010;12:1108-14 pubmed publisher
    ..we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif...
  29. Lin S, Chang D, Ying S, Leu D, Wu D. MicroRNA miR-302 inhibits the tumorigenecity of human pluripotent stem cells by coordinate suppression of the CDK2 and CDK4/6 cell cycle pathways. Cancer Res. 2010;70:9473-82 pubmed publisher
    ..we clarify this difference, reporting that in human cells, miR-302 simultaneously suppressed both the cyclin E-CDK2 and cyclin D-CDK4/6 pathways to block>70% of the G1-S cell cycle transition...
  30. Neganova I, Vilella F, Atkinson S, Lloret M, Passos J, von Zglinicki T, et al. An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells. Stem Cells. 2011;29:651-9 pubmed publisher
    ..Previously, we have shown that downregulation of cyclin-dependent kinase 2 (CDK2) in hESC causes G1 arrest, loss of pluripotency, upregulation of cell cycle inhibitors p21 and p27 and ..
  31. de Boer L, Oakes V, Beamish H, Giles N, Stevens F, Somodevilla Torres M, et al. Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events. Oncogene. 2008;27:4261-8 pubmed publisher
    Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G2 phase. Here we report that this G2 phase pool regulates the timing of progression into mitosis...
  32. Li Z, Pützer B. Spliceosomal protein E regulates neoplastic cell growth by modulating expression of cyclin E/CDK2 and G2/M checkpoint proteins. J Cell Mol Med. 2008;12:2427-38 pubmed publisher
    ..RT-PCR and immunoblotting showed that growth arrest by SmE directly correlates with the reduction of cyclin E, CDK2, CDC25C and CDC2 expression, and up-regulation of p27Kip...
  33. Driver K, Song H, Lesueur F, Ahmed S, Barbosa Morais N, Tyrer J, et al. Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population. Carcinogenesis. 2008;29:333-41 pubmed publisher
    ..Seventy-nine tag SNPs were used to evaluate 240 common SNPs found in the genes: CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKNIB, CDKN2A/CDKN2B, CDKN2C and CDKN2D...
  34. Hwang C, Lee S, Park S, Kwon K. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species. Biochem Biophys Res Commun. 2012;425:94-9 pubmed publisher
    ..cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence...
  35. Holmes J, Solomon M. The role of Thr160 phosphorylation of Cdk2 in substrate recognition. Eur J Biochem. 2001;268:4647-52 pubmed
    ..kinases (Cdks) requires binding to a cyclin and phosphorylation on an activating site equivalent to Thr160 in Cdk2 by the Cdk-activating kinase...
  36. Cheng A, Xiong W, Ferrell J, Solomon M. Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins. Cell Cycle. 2005;4:155-65 pubmed
    ..Of the mammalian proteins, two, Speedy/Ringo A and C, bind to Cdc2 and Cdk2, whereas Speedy/Ringo B binds preferentially to Cdc2...
  37. Chu I, Sun J, Arnaout A, Kahn H, Hanna W, Narod S, et al. p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2. Cell. 2007;128:281-94 pubmed
    ..Src-phosphorylated p27 is shown to inhibit cyclin E-Cdk2 poorly in vitro, and Src transfection reduces p27-cyclin E-Cdk2 complexes...
  38. Chytil A, Waltner Law M, West R, Friedman D, Aakre M, Barker D, et al. Construction of a cyclin D1-Cdk2 fusion protein to model the biological functions of cyclin D1-Cdk2 complexes. J Biol Chem. 2004;279:47688-98 pubmed
    ..Cyclin D1-Cdk2 complexes were previously observed in human breast cancer cell lines, but their role in cell cycle regulation and ..
  39. Kaldis P, Aleem E. Cell cycle sibling rivalry: Cdc2 vs. Cdk2. Cell Cycle. 2005;4:1491-4 pubmed
    It has been long believed that the cyclin-dependent kinase 2 (Cdk2) binds to cyclin E or cyclin A and exclusively promotes the G1/S phase transition and that Cdc2/cyclin B complexes play a major role in mitosis...
  40. Ammosova T, Berro R, Kashanchi F, Nekhai S. RNA interference directed to CDK2 inhibits HIV-1 transcription. Virology. 2005;341:171-8 pubmed
    We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro...
  41. Larochelle S, Merrick K, Terret M, Wohlbold L, Barboza N, Zhang C, et al. Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells. Mol Cell. 2007;25:839-50 pubmed
    ..In metazoans, S phase onset coincides with activation of Cdk2, whereas Cdk1 triggers mitosis...
  42. Garcia H, Brar G, Nguyen D, Bjeldanes L, Firestone G. Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. J Biol Chem. 2005;280:8756-64 pubmed
    Indole-3-carbinol (I3C), a dietary compound found in cruciferous vegetables, induces a robust inhibition of CDK2 specific kinase activity as part of a G1 cell cycle arrest of human breast cancer cells...
  43. Hydbring P, Bahram F, Su Y, Tronnersjö S, Högstrand K, von der Lehr N, et al. Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation. Proc Natl Acad Sci U S A. 2010;107:58-63 pubmed publisher
    ..b>Cdk2 interacted with Myc at promoters, where it affected Myc-dependent regulation of genes, including Bmi-1, p16, p21, ..
  44. Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M, Pagano M, et al. An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. Mol Cell. 2004;16:47-58 pubmed
    ..These results identify an Rb-Skp2-p27 pathway in Rb function, which may be involved in inhibition of tumor progression. ..
  45. Goode E, Fridley B, Vierkant R, Cunningham J, Phelan C, Anderson S, et al. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:935-44 pubmed publisher
    ..of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B)...
  46. Honda R, Lowe E, Dubinina E, Skamnaki V, Cook A, Brown N, et al. The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles. EMBO J. 2005;24:452-63 pubmed
    Cyclin E, an activator of phospho-CDK2 (pCDK2), is important for cell cycle progression in metazoans and is frequently overexpressed in cancer cells...
  47. Hayami R, Sato K, Wu W, Nishikawa T, Hiroi J, Ohtani Kaneko R, et al. Down-regulation of BRCA1-BARD1 ubiquitin ligase by CDK2. Cancer Res. 2005;65:6-10 pubmed
    ..Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2. During the cell cycle, BARD1 expression can largely be categorized into three patterns: moderately expressed in a ..
  48. Azzato E, Driver K, Lesueur F, Shah M, Greenberg D, Easton D, et al. Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohort. Breast Cancer Res. 2008;10:R47 pubmed publisher
    ..between common germline genetic variation in 13 genes involved in cell cycle control (CCND1, CCND2, CCND3, CCNE1, CDK2 [p33], CDK4, CDK6, CDKN1A [p21, Cip1], CDKN1B [p27, Kip1], CDKN2A [p16], CDKN2B [p15], CDKN2C [p18], and CDKN2D [..
  49. Larochelle S, Batliner J, Gamble M, Barboza N, Kraybill B, Blethrow J, et al. Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics. Nat Struct Mol Biol. 2006;13:55-62 pubmed
    ..Thus, Cdk7 accomplishes dual functions in cell-cycle control and transcription not through promiscuity but through distinct, stringent modes of substrate recognition. ..
  50. Terret M, Lefebvre C, Djiane A, Rassinier P, Moreau J, Maro B, et al. DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes. Development. 2003;130:5169-77 pubmed
    ..Thus, the discovery of DOC1R, a substrate of MAPK that regulates microtubule organization of metaphase II mouse oocytes, reinforces the importance of this pathway in the control of spindle stability during the metaphase II arrest. ..
  51. Buis J, Stoneham T, Spehalski E, Ferguson D. Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2. Nat Struct Mol Biol. 2012;19:246-52 pubmed publisher
    ..Here we show that, in human and mouse, Mre11 controls these events through a direct interaction with CDK2 that is required for CtIP phosphorylation and BRCA1 interaction in normally dividing cells...
  52. Porter L, Dellinger R, Tynan J, Barnes E, Kong M, Lenormand J, et al. Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2. J Cell Biol. 2002;157:357-66 pubmed
    ..Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of ..
  53. Han J, Wang H, Xie Y, Li Y, Zheng L, Ruan Y, et al. Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women. PLoS ONE. 2012;7:e49296 pubmed publisher
    Somatic alterations of cyclin-dependent kinase 2 (CDK2)-cyclin E complex have been shown to contribute to breast cancer (BC) development and progression...
  54. Myers J, Zhao R, Xu X, Ham A, Cortez D. Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer Res. 2007;67:6685-90 pubmed
    ..S224 matches a consensus site for cyclin-dependent kinase (CDK) phosphorylation and is phosphorylated by CDK2-cyclin A in vitro. S224 phosphorylation in cells is sensitive to CDK2 inhibitors...
  55. Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel E, Waddell M, et al. Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell. 2007;128:269-80 pubmed
    ..Y88 phosphorylation does not prevent p27 binding to cyclin A/Cdk2. Instead, it causes phosphorylated Y88 and the entire inhibitory 3(10)-helix of p27 to be ejected from the Cdk2 ..
  56. Welcker M, Singer J, Loeb K, Grim J, Bloecher A, Gurien West M, et al. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell. 2003;12:381-92 pubmed
    ..We show that assembly of cyclin E into cyclin E-Cdk2 complexes is required in vivo for turnover by the Fbw7 pathway; that Cdk2 activity is required for cyclin E ..
  57. Contreras A, Hale T, Stenoien D, Rosen J, Mancini M, Herrera R. The dynamic mobility of histone H1 is regulated by cyclin/CDK phosphorylation. Mol Cell Biol. 2003;23:8626-36 pubmed
    ..Cyclin E/CDK2 or cyclin A/CDK2 cannot phosphorylate the mutant in vitro...
  58. Diederichs S, Baumer N, Ji P, Metzelder S, Idos G, Cauvet T, et al. Identification of interaction partners and substrates of the cyclin A1-CDK2 complex. J Biol Chem. 2004;279:33727-41 pubmed
    The CDK2-associated cyclin A1 is essential for spermatogenesis and contributes to leukemogenesis. The detailed molecular functions of cyclin A1 remain unclear, since the molecular networks involving cyclin A1-CDK2 have not been elucidated...
  59. Baydoun H, Pancewicz J, Bai X, Nicot C. HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression. Mol Cancer. 2010;9:302 pubmed publisher
    ..We found that p30 binds to cyclin E and CDK2 and prevents the formation of active cyclin E-CDK2 complexes...
  60. Calbo J, Serna C, Garriga J, Grana X, Mazo A. The fate of pancreatic tumor cell lines following p16 overexpression depends on the modulation of CDK2 activity. Cell Death Differ. 2004;11:1055-65 pubmed
    ..of p16 leads to G1 arrest in NP-9 cells by redistributing p21/p27 CKIs and inhibiting cyclin-dependent kinase CDK2 activity...
  61. Falck J, Petrini J, Williams B, Lukas J, Bartek J. The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat Genet. 2002;30:290-4 pubmed
    ..3), the Nbs1-interacting Mre11 protein, or the Chk2-regulated Cdc25A-Cdk2 cascade all cause radio-resistant DNA synthesis (RDS)...
  62. Chung J, Bunz F. Cdk2 is required for p53-independent G2/M checkpoint control. PLoS Genet. 2010;6:e1000863 pubmed publisher
    ..Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice...
  63. Mateo F, Vidal Laliena M, Canela N, Busino L, Martinez Balbas M, Pagano M, et al. Degradation of cyclin A is regulated by acetylation. Oncogene. 2009;28:2654-66 pubmed publisher
    ..All these results indicate that cyclin A acetylation at specific lysines is crucial for cyclin A stability and also has a function in the regulation of cycA-cdk activity. ..
  64. Nevis K, Cordeiro Stone M, Cook J. Origin licensing and p53 status regulate Cdk2 activity during G(1). Cell Cycle. 2009;8:1952-63 pubmed
    ..factors, Cdc6 or Cdt1, in normal human fibroblasts induces a G(1) arrest accompanied by inhibition of cyclin E/Cdk2 activity and hypophosphorylation of Rb...
  65. Sotillo E, Garriga J, Padgaonkar A, Kurimchak A, Cook J, Grana X. Coordinated activation of the origin licensing factor CDC6 and CDK2 in resting human fibroblasts expressing SV40 small T antigen and cyclin E. J Biol Chem. 2009;284:14126-35 pubmed publisher
    We have previously shown that SV40 small t antigen (st) cooperates with deregulated cyclin E to activate CDK2 and bypass quiescence in normal human fibroblasts (NHF)...
  66. Gao D, Inuzuka H, Tseng A, Chin R, Toker A, Wei W. Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction. Nat Cell Biol. 2009;11:397-408 pubmed publisher
  67. Song H, Hogdall E, Ramus S, Dicioccio R, Hogdall C, Quaye L, et al. Effects of common germ-line genetic variation in cell cycle genes on ovarian cancer survival. Clin Cancer Res. 2008;14:1090-5 pubmed publisher
    ..genes involved in cell cycle pathway (CCND1, CCND2, CCND3, CCNE1, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDK2, CDK4, CDK6, and RB1) and survival among women with invasive ovarian cancer participating in a multicenter case-..
  68. Deans A, Khanna K, McNees C, Mercurio C, Heierhorst J, McArthur G. Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers. Cancer Res. 2006;66:8219-26 pubmed
    ..However, inhibition of CDKs, particularly CDK2, has not shown selective activity against most cancer cells because the kinase seems to be redundant in control of ..
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