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Gene Review

Ccne1  -  cyclin E1

Rattus norvegicus

Synonyms: CYCLE, Ccne, G1/S-specific cyclin-E1
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Disease relevance of Ccne1


High impact information on Ccne1


Chemical compound and disease context of Ccne1

  • Here, we show that DHEA is a liver mitogen, increasing proliferation in rat liver after 3 days of treatment (100 mg/kg body weight per day) as indicated by significantly enhanced expression of cyclin E, PCNA and Ki-67 and an elevated number of mitotic figures [9].

Biological context of Ccne1


Anatomical context of Ccne1


Associations of Ccne1 with chemical compounds

  • Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide [18].
  • The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho [15].
  • In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition [15].
  • Since serum-induced expression of cyclin E was also suppressed by inostamycin, this inhibitor would appear to block CDK2 activation by inhibiting cyclin E expression [19].
  • The addition of SNP or SNAP to VSMC cultures at the time of serum stimulation abrogates the induction of cdk2 activity without suppressing protein levels of cdk2 or cyclin E. These NO donors block serum-stimulated upregulation of cyclin A mRNA and protein and repress the serum induction of cyclin A promoter activity in VSMCs [20].

Physical interactions of Ccne1


Enzymatic interactions of Ccne1

  • Cyclin D1 and phosphorylated cyclin E accumulated at 12 h but were degraded by 24 h after addition of EGF [22].

Regulatory relationships of Ccne1

  • These experiments revealed that deregulated E2F-1 expression triggers high levels of cyclin E and A expression and kinase activities in small early G1 cells, normally not exhibiting these activities [23].
  • Under these conditions, CDK2 and CDK4 protein expression remained unchanged compared with proliferating cells, but expression of cyclin D1 and p27(KIP1) was down-regulated and cyclin E accumulated in the inactive form [22].
  • Cyclin E is significantly up-regulated during the extracellular matrix mineralization developmental period [16].
  • The marked increments in mRNA expression and protein synthesis of cyclin E induced by TNF-alpha in parallel with proliferation of mesangial cells were down-regulated by LXA(4) [24].

Other interactions of Ccne1

  • In contrast, the protein amounts of Cdk2, cyclin D1, and cyclin E were not changed by repeated ECS [25].
  • Other cyclins, including cyclin B and cyclin E, were not induced [26].
  • The present study demonstrates that the genes of cyclin E, cdk2, cdk5 and the transcriptional factor E2F-1 are expressed during the prolactin (PRL)-induced G1/S transition in rat Nb2 pre-T lymphoma cells [14].
  • The induction of Cdk4 expression and activity is also markedly attenuated, which likely contributes to the inhibition of cyclin E expression [27].
  • However, inhibition of p38 MAPKs by SB203580 was without effect on total cyclin E and Cdk2 levels [28].

Analytical, diagnostic and therapeutic context of Ccne1


  1. The oncogenic activity of cyclin E is not confined to Cdk2 activation alone but relies on several other, distinct functions of the protein. Geisen, C., Moroy, T. J. Biol. Chem. (2002) [Pubmed]
  2. Overexpression of protein kinase G using adenovirus inhibits cyclin E transcription and mesangial cell cycle. Hanada, S., Terada, Y., Inoshita, S., Sasaki, S., Lohmann, S.M., Smolenski, A., Marumo, F. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  3. Aberrant expression of p27(Kip1) is associated with malignant transformation of the rat urinary bladder epithelium. Ogawa, K., Kimoto, N., Asamoto, M., Nakanishi, M., Takahashi, S., Shirai, T. Carcinogenesis (2000) [Pubmed]
  4. Lower activity of CCAAT/enhancer-binding protein and expression of cyclin E, but not cyclin D1, activating protein-1 and p21(WAF1), after partial hepatectomy in obstructive jaundice. Nakano, K., Chijiiwa, K., Tanaka, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  5. Inhibition of DNA synthesis by RB: effects on G1/S transition and S-phase progression. Knudsen, E.S., Buckmaster, C., Chen, T.T., Feramisco, J.R., Wang, J.Y. Genes Dev. (1998) [Pubmed]
  6. A K-ras oncogene increases resistance to sulindac-induced apoptosis in rat enterocytes. Arber, N., Han, E.K., Sgambato, A., Piazza, G.A., Delohery, T.M., Begemann, M., Weghorst, C.M., Kim, N.H., Pamukcu, R., Ahnen, D.J., Reed, J.C., Weinstein, I.B., Holt, P.R. Gastroenterology (1997) [Pubmed]
  7. E1A can provoke G1 exit that is refractory to p21 and independent of activating cdk2. Akli, S., Zhan, S., Abdellatif, M., Schneider, M.D. Circ. Res. (1999) [Pubmed]
  8. Ectopic expression of cyclin D1 but not cyclin E induces anchorage-independent cell cycle progression. Resnitzky, D. Mol. Cell. Biol. (1997) [Pubmed]
  9. Dehydroepiandrosterone causes hyperplasia and impairs regeneration in rat liver. Kopplow, K., Wayss, K., Enzmann, H., Mayer, D. Int. J. Oncol. (2005) [Pubmed]
  10. Long-term 17alpha-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver. Koroxenidou, L., Ohlson, L.C., Porsch Hällström, I. J. Hepatol. (2005) [Pubmed]
  11. Lack of intestinal bile results in delayed liver regeneration of normal rat liver after hepatectomy accompanied by impaired cyclin E-associated kinase activity. Ueda, J., Chijiiwa, K., Nakano, K., Zhao, G., Tanaka, M. Surgery (2002) [Pubmed]
  12. Basic fibroblast growth factor exhibits dual and rapid regulation of cyclin D1 and p27 to stimulate proliferation of rat cerebral cortical precursors. Li, B., DiCicco-Bloom, E. Dev. Neurosci. (2004) [Pubmed]
  13. A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry. Matsumoto, Y., Maller, J.L. Science (2004) [Pubmed]
  14. Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells. Hosokawa, Y., Yang, M., Kaneko, S., Tanaka, M., Nakashima, K. Biochem. Mol. Biol. Int. (1995) [Pubmed]
  15. Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes. Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression. Tanaka, T., Tatsuno, I., Noguchi, Y., Uchida, D., Oeda, T., Narumiya, S., Yasuda, T., Higashi, H., Kitagawa, M., Nakayama, K., Saito, Y., Hirai, A. J. Biol. Chem. (1998) [Pubmed]
  16. Expression of cell cycle regulatory factors in differentiating osteoblasts: postproliferative up-regulation of cyclins B and E. Smith, E., Frenkel, B., Schlegel, R., Giordano, A., Lian, J.B., Stein, J.L., Stein, G.S. Cancer Res. (1995) [Pubmed]
  17. Characterization of Cdk2-cyclin E complexes in plasma membrane and endosomes of liver parenchyma. Insulin-dependent regulation. Gaulin, J.F., Fiset, A., Fortier, S., Faure, R.L. J. Biol. Chem. (2000) [Pubmed]
  18. Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide. Kim, K.T., Han, S.Y., Jeong, J.S. The Korean journal of hepatology (2007) [Pubmed]
  19. Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor. Deguchi, A., Imoto, M., Umezawa, K. J. Biochem. (1996) [Pubmed]
  20. Nitric oxide-induced downregulation of Cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells. Guo, K., Andrés, V., Walsh, K. Circulation (1998) [Pubmed]
  21. Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27(Kip1) binding to newly formed complexes. Pérez-Roger, I., Solomon, D.L., Sewing, A., Land, H. Oncogene (1997) [Pubmed]
  22. G1-arrested FaO cells re-enter the cell cycle upon stimulation with the rodent non-genotoxic hepatocarcinogen nafenopin. Chevalier, S., Roberts, R.A. Carcinogenesis (1999) [Pubmed]
  23. Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position. Soucek, T., Pusch, O., Hengstschläger-Ottnad, E., Adams, P.D., Hengstschläger, M. Oncogene (1997) [Pubmed]
  24. Lipoxin A4 inhibits TNF-alpha-induced production of interleukins and proliferation of rat mesangial cells. Wu, S.H., Lu, C., Dong, L., Zhou, G.P., He, Z.G., Chen, Z.Q. Kidney Int. (2005) [Pubmed]
  25. Activation of Cdk2-pRB-E2F1 cell cycle pathway by repeated electroconvulsive shock in the rat frontal cortex. Kim, Y., Seo, M.S., Kang, U.G., Yoon, S.C., Ahn, Y.M., Kim, Y.S., Juhnn, Y.S. Biol. Psychiatry (2005) [Pubmed]
  26. Cyclin D1 is up-regulated in hepatocytes in vivo following cell-cycle block induced by retrorsine. Pitzalis, S., Doratiotto, S., Greco, M., Montisci, S., Pasciu, D., Porcu, G., Pani, P., Laconi, S., Laconi, E. J. Hepatol. (2005) [Pubmed]
  27. Expression of angiotensin type II receptor downregulates Cdk4 synthesis and inhibits cell-cycle progression. Gingras, B., Rodier, G., Giasson, E., Coulombe, P., Chassagne, C., Meloche, S. Oncogene (2003) [Pubmed]
  28. p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells. Corrèze, C., Blondeau, J.P., Pomérance, M. Eur. J. Endocrinol. (2005) [Pubmed]
  29. After portal branch ligation in the rat, cellular proliferation is associated with selective induction of c-Ha-ras, p53, cyclin E, and Cdk2. Stärkel, P., Lambotte, L., Sempoux, C., De Saeger, C., Saliez, A., Maiter, D., Horsmans, Y. Gut (2001) [Pubmed]
  30. Retinoic acid-induced proliferation of lung alveolar epithelial cells is linked to p21(CIP1) downregulation. Nabeyrat, E., Corroyer, S., Epaud, R., Besnard, V., Cazals, V., Clement, A. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  31. Increased expression of cyclin D1, cyclin E and p21(Cip1) associated with decreased expression of p27(Kip1) in chemically induced rat mammary carcinogenesis. Jang, T.J., Kang, M.S., Kim, H., Kim, D.H., Lee, J.I., Kim, J.R. Jpn. J. Cancer Res. (2000) [Pubmed]
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