Skip to main content
Genetics logoLink to Genetics
. 2000 May;155(1):233–244. doi: 10.1093/genetics/155.1.233

A screen for modifiers of cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2.

M E Lane 1, M Elend 1, D Heidmann 1, A Herr 1, S Marzodko 1, A Herzig 1, C F Lehner 1
PMCID: PMC1461066  PMID: 10790398

Abstract

In 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. To identify genes interacting with cyclin E, we have screened in Drosophila melanogaster for mutations that act as dominant modifiers of an eye phenotype caused by a Sevenless-CycE transgene that directs ectopic Cyclin E expression in postmitotic cells of eye imaginal disc and causes a rough eye phenotype in adult flies. The majority of the EMS-induced mutations that we have identified fall into four complementation groups corresponding to the genes split ends, dacapo, dE2F1, and Cdk2(Cdc2c). The Cdk2 mutations in combination with mutant Cdk2 transgenes have allowed us to address the regulatory significance of potential phosphorylation sites in Cdk2 (Thr 18 and Tyr 19). The corresponding sites in the closely related Cdk1 (Thr 14 and Tyr 15) are of crucial importance for regulation of the G2/M transition by myt1 and wee1 kinases and cdc25 phosphatases. In contrast, our results demonstrate that the equivalent sites in Cdk2 play no essential role.

Full Text

The Full Text of this article is available as a PDF (525.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asano M., Wharton R. P. E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila. EMBO J. 1999 May 4;18(9):2435–2448. doi: 10.1093/emboj/18.9.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Basler K., Christen B., Hafen E. Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye. Cell. 1991 Mar 22;64(6):1069–1081. doi: 10.1016/0092-8674(91)90262-w. [DOI] [PubMed] [Google Scholar]
  3. Bier E., Vaessin H., Shepherd S., Lee K., McCall K., Barbel S., Ackerman L., Carretto R., Uemura T., Grell E. Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 1989 Sep;3(9):1273–1287. doi: 10.1101/gad.3.9.1273. [DOI] [PubMed] [Google Scholar]
  4. Brehm A., Miska E. A., McCance D. J., Reid J. L., Bannister A. J., Kouzarides T. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature. 1998 Feb 5;391(6667):597–601. doi: 10.1038/35404. [DOI] [PubMed] [Google Scholar]
  5. Clurman B. E., Sheaff R. J., Thress K., Groudine M., Roberts J. M. Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev. 1996 Aug 15;10(16):1979–1990. doi: 10.1101/gad.10.16.1979. [DOI] [PubMed] [Google Scholar]
  6. Du W., Dyson N. The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. EMBO J. 1999 Feb 15;18(4):916–925. doi: 10.1093/emboj/18.4.916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Du W., Vidal M., Xie J. E., Dyson N. RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev. 1996 May 15;10(10):1206–1218. doi: 10.1101/gad.10.10.1206. [DOI] [PubMed] [Google Scholar]
  8. Dulić V., Lees E., Reed S. I. Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 1992 Sep 25;257(5078):1958–1961. doi: 10.1126/science.1329201. [DOI] [PubMed] [Google Scholar]
  9. Duronio R. J., Bonnette P. C., O'Farrell P. H. Mutations of the Drosophila dDP, dE2F, and cyclin E genes reveal distinct roles for the E2F-DP transcription factor and cyclin E during the G1-S transition. Mol Cell Biol. 1998 Jan;18(1):141–151. doi: 10.1128/mcb.18.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duronio R. J., Brook A., Dyson N., O'Farrell P. H. E2F-induced S phase requires cyclin E. Genes Dev. 1996 Oct 1;10(19):2505–2513. doi: 10.1101/gad.10.19.2505. [DOI] [PubMed] [Google Scholar]
  11. Duronio R. J., O'Farrell P. H. Developmental control of the G1 to S transition in Drosophila: cyclin Eis a limiting downstream target of E2F. Genes Dev. 1995 Jun 15;9(12):1456–1468. doi: 10.1101/gad.9.12.1456. [DOI] [PubMed] [Google Scholar]
  12. Duronio R. J., O'Farrell P. H., Xie J. E., Brook A., Dyson N. The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev. 1995 Jun 15;9(12):1445–1455. doi: 10.1101/gad.9.12.1445. [DOI] [PubMed] [Google Scholar]
  13. Dynlacht B. D., Brook A., Dembski M., Yenush L., Dyson N. DNA-binding and trans-activation properties of Drosophila E2F and DP proteins. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6359–6363. doi: 10.1073/pnas.91.14.6359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998 Aug 1;12(15):2245–2262. doi: 10.1101/gad.12.15.2245. [DOI] [PubMed] [Google Scholar]
  15. Field S. J., Tsai F. Y., Kuo F., Zubiaga A. M., Kaelin W. G., Jr, Livingston D. M., Orkin S. H., Greenberg M. E. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell. 1996 May 17;85(4):549–561. doi: 10.1016/s0092-8674(00)81255-6. [DOI] [PubMed] [Google Scholar]
  16. Gellon G., Harding K. W., McGinnis N., Martin M. M., McGinnis W. A genetic screen for modifiers of Deformed homeotic function identifies novel genes required for head development. Development. 1997 Sep;124(17):3321–3331. doi: 10.1242/dev.124.17.3321. [DOI] [PubMed] [Google Scholar]
  17. Geng Y., Whoriskey W., Park M. Y., Bronson R. T., Medema R. H., Li T., Weinberg R. A., Sicinski P. Rescue of cyclin D1 deficiency by knockin cyclin E. Cell. 1999 Jun 11;97(6):767–777. doi: 10.1016/s0092-8674(00)80788-6. [DOI] [PubMed] [Google Scholar]
  18. Gu Y., Rosenblatt J., Morgan D. O. Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. EMBO J. 1992 Nov;11(11):3995–4005. doi: 10.1002/j.1460-2075.1992.tb05493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hao X. F., Alphey L., Bandara L. R., Lam E. W., Glover D., La Thangue N. B. Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. J Cell Sci. 1995 Sep;108(Pt 9):2945–2954. doi: 10.1242/jcs.108.9.2945. [DOI] [PubMed] [Google Scholar]
  20. Harbour J. W., Luo R. X., Dei Santi A., Postigo A. A., Dean D. C. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell. 1999 Sep 17;98(6):859–869. doi: 10.1016/s0092-8674(00)81519-6. [DOI] [PubMed] [Google Scholar]
  21. Hinchcliffe E. H., Li C., Thompson E. A., Maller J. L., Sluder G. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. Science. 1999 Feb 5;283(5403):851–854. doi: 10.1126/science.283.5403.851. [DOI] [PubMed] [Google Scholar]
  22. Hinds P. W., Mittnacht S., Dulic V., Arnold A., Reed S. I., Weinberg R. A. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. doi: 10.1016/0092-8674(92)90249-c. [DOI] [PubMed] [Google Scholar]
  23. Hoffmann I., Draetta G., Karsenti E. Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J. 1994 Sep 15;13(18):4302–4310. doi: 10.1002/j.1460-2075.1994.tb06750.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hua X. H., Newport J. Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2. J Cell Biol. 1998 Jan 26;140(2):271–281. doi: 10.1083/jcb.140.2.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hua X. H., Yan H., Newport J. A role for Cdk2 kinase in negatively regulating DNA replication during S phase of the cell cycle. J Cell Biol. 1997 Apr 7;137(1):183–192. doi: 10.1083/jcb.137.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jackson P. K., Chevalier S., Philippe M., Kirschner M. W. Early events in DNA replication require cyclin E and are blocked by p21CIP1. J Cell Biol. 1995 Aug;130(4):755–769. doi: 10.1083/jcb.130.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jinno S., Suto K., Nagata A., Igarashi M., Kanaoka Y., Nojima H., Okayama H. Cdc25A is a novel phosphatase functioning early in the cell cycle. EMBO J. 1994 Apr 1;13(7):1549–1556. doi: 10.1002/j.1460-2075.1994.tb06417.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Johnston L. A., Edgar B. A. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature. 1998 Jul 2;394(6688):82–84. doi: 10.1038/27925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Karr T. L. Intracellular sperm/egg interactions in Drosophila: a three-dimensional structural analysis of a paternal product in the developing egg. Mech Dev. 1991 Jun;34(2-3):101–111. doi: 10.1016/0925-4773(91)90047-a. [DOI] [PubMed] [Google Scholar]
  30. Kelly B. L., Wolfe K. G., Roberts J. M. Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2535–2540. doi: 10.1073/pnas.95.5.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kim S. H., Li C., Maller J. L. A maternal form of the phosphatase Cdc25A regulates early embryonic cell cycles in Xenopus laevis. Dev Biol. 1999 Aug 15;212(2):381–391. doi: 10.1006/dbio.1999.9361. [DOI] [PubMed] [Google Scholar]
  32. Kitagawa M., Higashi H., Jung H. K., Suzuki-Takahashi I., Ikeda M., Tamai K., Kato J., Segawa K., Yoshida E., Nishimura S. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996 Dec 16;15(24):7060–7069. [PMC free article] [PubMed] [Google Scholar]
  33. Knoblich J. A., Sauer K., Jones L., Richardson H., Saint R., Lehner C. F. Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Cell. 1994 Apr 8;77(1):107–120. doi: 10.1016/0092-8674(94)90239-9. [DOI] [PubMed] [Google Scholar]
  34. Koff A., Giordano A., Desai D., Yamashita K., Harper J. W., Elledge S., Nishimoto T., Morgan D. O., Franza B. R., Roberts J. M. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 1992 Sep 18;257(5077):1689–1694. doi: 10.1126/science.1388288. [DOI] [PubMed] [Google Scholar]
  35. Kolodziej P. A., Jan L. Y., Jan Y. N. Mutations that affect the length, fasciculation, or ventral orientation of specific sensory axons in the Drosophila embryo. Neuron. 1995 Aug;15(2):273–286. doi: 10.1016/0896-6273(95)90033-0. [DOI] [PubMed] [Google Scholar]
  36. Kuang B., Wu S. C., Shin Y., Luo L., Kolodziej P. split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo. Development. 2000 Apr;127(7):1517–1529. doi: 10.1242/dev.127.7.1517. [DOI] [PubMed] [Google Scholar]
  37. Lacey K. R., Jackson P. K., Stearns T. Cyclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2817–2822. doi: 10.1073/pnas.96.6.2817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lane M. E., Sauer K., Wallace K., Jan Y. N., Lehner C. F., Vaessin H. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell. 1996 Dec 27;87(7):1225–1235. doi: 10.1016/s0092-8674(00)81818-8. [DOI] [PubMed] [Google Scholar]
  39. Lehner C. F., O'Farrell P. H. Drosophila cdc2 homologs: a functional homolog is coexpressed with a cognate variant. EMBO J. 1990 Nov;9(11):3573–3581. doi: 10.1002/j.1460-2075.1990.tb07568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lehner C. F., O'Farrell P. H. Expression and function of Drosophila cyclin A during embryonic cell cycle progression. Cell. 1989 Mar 24;56(6):957–968. doi: 10.1016/0092-8674(89)90629-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lehner C. F., Yakubovich N., O'Farrell P. H. Exploring the role of Drosophila cyclin A in the regulation of S phase. Cold Spring Harb Symp Quant Biol. 1991;56:465–475. doi: 10.1101/sqb.1991.056.01.053. [DOI] [PubMed] [Google Scholar]
  42. Leng X., Connell-Crowley L., Goodrich D., Harper J. W. S-Phase entry upon ectopic expression of G1 cyclin-dependent kinases in the absence of retinoblastoma protein phosphorylation. Curr Biol. 1997 Sep 1;7(9):709–712. doi: 10.1016/s0960-9822(06)00301-0. [DOI] [PubMed] [Google Scholar]
  43. Lew D. J., Dulić V., Reed S. I. Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell. 1991 Sep 20;66(6):1197–1206. doi: 10.1016/0092-8674(91)90042-w. [DOI] [PubMed] [Google Scholar]
  44. Lukas J., Herzinger T., Hansen K., Moroni M. C., Resnitzky D., Helin K., Reed S. I., Bartek J. Cyclin E-induced S phase without activation of the pRb/E2F pathway. Genes Dev. 1997 Jun 1;11(11):1479–1492. doi: 10.1101/gad.11.11.1479. [DOI] [PubMed] [Google Scholar]
  45. Lundberg A. S., Weinberg R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 1998 Feb;18(2):753–761. doi: 10.1128/mcb.18.2.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Luo R. X., Postigo A. A., Dean D. C. Rb interacts with histone deacetylase to repress transcription. Cell. 1998 Feb 20;92(4):463–473. doi: 10.1016/s0092-8674(00)80940-x. [DOI] [PubMed] [Google Scholar]
  47. Magnaghi-Jaulin L., Groisman R., Naguibneva I., Robin P., Lorain S., Le Villain J. P., Troalen F., Trouche D., Harel-Bellan A. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature. 1998 Feb 5;391(6667):601–605. doi: 10.1038/35410. [DOI] [PubMed] [Google Scholar]
  48. Mittnacht S. Control of pRB phosphorylation. Curr Opin Genet Dev. 1998 Feb;8(1):21–27. doi: 10.1016/s0959-437x(98)80057-9. [DOI] [PubMed] [Google Scholar]
  49. Montagnoli A., Fiore F., Eytan E., Carrano A. C., Draetta G. F., Hershko A., Pagano M. Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation. Genes Dev. 1999 May 1;13(9):1181–1189. doi: 10.1101/gad.13.9.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ohtani K., Nevins J. R. Functional properties of a Drosophila homolog of the E2F1 gene. Mol Cell Biol. 1994 Mar;14(3):1603–1612. doi: 10.1128/mcb.14.3.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pirrotta V. Vectors for P-mediated transformation in Drosophila. Biotechnology. 1988;10:437–456. doi: 10.1016/b978-0-409-90042-2.50028-3. [DOI] [PubMed] [Google Scholar]
  52. Resnitzky D., Reed S. I. Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol Cell Biol. 1995 Jul;15(7):3463–3469. doi: 10.1128/mcb.15.7.3463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Richardson H. E., O'Keefe L. V., Reed S. I., Saint R. A Drosophila G1-specific cyclin E homolog exhibits different modes of expression during embryogenesis. Development. 1993 Nov;119(3):673–690. doi: 10.1242/dev.119.3.673. [DOI] [PubMed] [Google Scholar]
  54. Richardson H., O'Keefe L. V., Marty T., Saint R. Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc. Development. 1995 Oct;121(10):3371–3379. doi: 10.1242/dev.121.10.3371. [DOI] [PubMed] [Google Scholar]
  55. Royzman I., Whittaker A. J., Orr-Weaver T. L. Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. Genes Dev. 1997 Aug 1;11(15):1999–2011. doi: 10.1101/gad.11.15.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Royzman I., Whittaker A. J., Orr-Weaver T. L. Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. Genes Dev. 1997 Aug 1;11(15):1999–2011. doi: 10.1101/gad.11.15.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sauer K., Knoblich J. A., Richardson H., Lehner C. F. Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. Genes Dev. 1995 Jun 1;9(11):1327–1339. doi: 10.1101/gad.9.11.1327. [DOI] [PubMed] [Google Scholar]
  58. Sawado T., Yamaguchi M., Nishimoto Y., Ohno K., Sakaguchi K., Matsukage A. dE2F2, a novel E2F-family transcription factor in Drosophila melanogaster. Biochem Biophys Res Commun. 1998 Oct 20;251(2):409–415. doi: 10.1006/bbrc.1998.9407. [DOI] [PubMed] [Google Scholar]
  59. Sexl V., Diehl J. A., Sherr C. J., Ashmun R., Beach D., Roussel M. F. A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2. Oncogene. 1999 Jan 21;18(3):573–582. doi: 10.1038/sj.onc.1202362. [DOI] [PubMed] [Google Scholar]
  60. Sheaff R. J., Groudine M., Gordon M., Roberts J. M., Clurman B. E. Cyclin E-CDK2 is a regulator of p27Kip1. Genes Dev. 1997 Jun 1;11(11):1464–1478. doi: 10.1101/gad.11.11.1464. [DOI] [PubMed] [Google Scholar]
  61. Spradling A. C., Stern D. M., Kiss I., Roote J., Laverty T., Rubin G. M. Gene disruptions using P transposable elements: an integral component of the Drosophila genome project. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10824–10830. doi: 10.1073/pnas.92.24.10824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sprenger F., Yakubovich N., O'Farrell P. H. S-phase function of Drosophila cyclin A and its downregulation in G1 phase. Curr Biol. 1997 Jul 1;7(7):488–499. doi: 10.1016/s0960-9822(06)00220-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Staehling-Hampton K., Ciampa P. J., Brook A., Dyson N. A genetic screen for modifiers of E2F in Drosophila melanogaster. Genetics. 1999 Sep;153(1):275–287. doi: 10.1093/genetics/153.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stern B., Ried G., Clegg N. J., Grigliatti T. A., Lehner C. F. Genetic analysis of the Drosophila cdc2 homolog. Development. 1993 Jan;117(1):219–232. doi: 10.1242/dev.117.1.219. [DOI] [PubMed] [Google Scholar]
  65. Strausfeld U. P., Howell M., Descombes P., Chevalier S., Rempel R. E., Adamczewski J., Maller J. L., Hunt T., Blow J. J. Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts. J Cell Sci. 1996 Jun;109(Pt 6):1555–1563. doi: 10.1242/jcs.109.6.1555. [DOI] [PubMed] [Google Scholar]
  66. Thomas B. J., Gunning D. A., Cho J., Zipursky L. Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1. Cell. 1994 Jul 1;77(7):1003–1014. doi: 10.1016/0092-8674(94)90440-5. [DOI] [PubMed] [Google Scholar]
  67. Vlach J., Hennecke S., Amati B. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 1997 Sep 1;16(17):5334–5344. doi: 10.1093/emboj/16.17.5334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wang Z., Lindquist S. Developmentally regulated nuclear transport of transcription factors in Drosophila embryos enable the heat shock response. Development. 1998 Dec;125(23):4841–4850. doi: 10.1242/dev.125.23.4841. [DOI] [PubMed] [Google Scholar]
  69. Weinberg R. A. The retinoblastoma protein and cell cycle control. Cell. 1995 May 5;81(3):323–330. doi: 10.1016/0092-8674(95)90385-2. [DOI] [PubMed] [Google Scholar]
  70. Wiellette E. L., Harding K. W., Mace K. A., Ronshaugen M. R., Wang F. Y., McGinnis W. spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk. Development. 1999 Dec;126(23):5373–5385. doi: 10.1242/dev.126.23.5373. [DOI] [PubMed] [Google Scholar]
  71. Xu X., Burke S. P. Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25. J Biol Chem. 1996 Mar 1;271(9):5118–5124. doi: 10.1074/jbc.271.9.5118. [DOI] [PubMed] [Google Scholar]
  72. Yamasaki L., Jacks T., Bronson R., Goillot E., Harlow E., Dyson N. J. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell. 1996 May 17;85(4):537–548. doi: 10.1016/s0092-8674(00)81254-4. [DOI] [PubMed] [Google Scholar]
  73. Zhang H. S., Postigo A. A., Dean D. C. Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell. 1999 Apr 2;97(1):53–61. doi: 10.1016/s0092-8674(00)80714-x. [DOI] [PubMed] [Google Scholar]
  74. de Nooij J. C., Letendre M. A., Hariharan I. K. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell. 1996 Dec 27;87(7):1237–1247. doi: 10.1016/s0092-8674(00)81819-x. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES