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Gene Review

Ccnb1  -  cyclin B1

Rattus norvegicus

Synonyms: G2/mitotic-specific cyclin-B1
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Disease relevance of Ccnb1

  • A statistically sixfold lower expression of Rasgrf2 was detected in carcinomas whereas no significant change in Ccnb1 expression was observed [1].
  • These results indicate that aberrant expression of cdk4, but not cyclin B1, cyclin D1 or PCNA, actually takes place in the brain after MCA occlusion, but this is not the causative mechanism of apoptotic cell death in the brain with ischemia [2].
  • These data demonstrate that Cks1 regulates cyclin B metabolism and ploidy in VSMC and may contribute to the understanding of the phenomena of VSMC polyploidization during hypertension [3].
  • Finally, transduction of VSMC from normotensive animals with a retrovirus that drives the expression of Cks1 was sufficient to alter their mitotic spindle cell cycle checkpoint status and promote unscheduled cyclin B metabolism, cell cycle re-entry, and polyploidization [3].
  • In diabetic rats there was jejunal hyperplasia as indicated by increases in the jejunal mucosal weight/cm and DNA content as well as increased activities of MAP-K and p34cdc2 kinase and association of the latter with cyclin B as compared to corresponding values in control rats [4].

High impact information on Ccnb1

  • Similar results were obtained with the homogeneous catalytic subunit of p34cdc2 kinase or p34cdc2 kinase associated with cyclin B. These alterations were accompanied by a marked reduction in interphase microtubules without the spindle formation, actin microfilament redistribution, and premature chromatin condensation [5].
  • The ability of the anaphase-promoting complex/cyclosome (APC), an E3 ubiquitin ligase, to trigger cyclin B destruction and metaphase exit is blocked in eggs by the activity of cytostatic factor (CSF) (reviewed in ref. 1). CSF was defined as an activity in mature oocytes that caused mitotic arrest when injected into dividing embryos [6].
  • Vertebrate eggs are arrested at metaphase of meiosis II with stable cyclin B and high cyclin B/Cdc2 kinase activity [6].
  • Finally, the kinetics of B-Myb interaction with the G2-regulated promoters coincides with the activation of the genes, and RNAi-mediated reduction of B-Myb inhibits expression of cyclin B1 and cdc2 [7].
  • Through association with CDK1, cyclin B accumulation and destruction govern the G2/M/G1 transitions in eukaryotic cells [8].

Chemical compound and disease context of Ccnb1


Biological context of Ccnb1

  • PURPOSE: To evaluate the hypothesis that the radiation induced G2 delay in the cell cycle is associated with radiation induced effects on cyclin B expression in a rodent cell system [9].
  • Our studies show that rat cyclin B expression is influenced by radiation and is temporally related to the delay in the G2 phase induced by radiation [9].
  • Selective degradation of cyclin B1 mRNA in rat oocytes by RNA interference (RNAi) [10].
  • The failure of IGF-1 to enhance cyclin B kinase activity may be responsible for a block in the cell cycle and the inability of myocytes to progress through the M phase and subsequently divide [11].
  • Cyclin D1 mRNA levels were elevated 8 and 10 h after estradiol administration, corresponding to the G1 phase of the mitotic cycle, and cyclin B1 mRNA was only expressed 16-24 h after estradiol treatment, which corresponds to the G2 and M phases of the rat uterine epithelial cell cycle [12].

Anatomical context of Ccnb1

  • We demonstrated that the introduction of cyclin B1 dsRNA into rat oocytes selectively depleted the corresponding mRNA, further ablating its protein product [10].
  • The elevation of nuclear cyclin E and cytoplasmic cyclin B is not observed in osteoblasts maintained under culture conditions that do not support differentiation [13].
  • EGF alone stimulated proliferation of PC12 cells and increased the levels of several cell cycle progression factors including cdk2, cdk4, and cyclin B1 [14].
  • Cks1 up-regulation, cyclin B down-regulation, and VSMC polyploidization were evidenced at the smooth muscle of capacitance arteries of genetically hypertensive and Goldblatt-operated rats [3].
  • Immunohistochemical studies on postmortem brains revealed intense cyclin B immunoreactivity in Lewy bodies in cases with DLB and to a lesser extent in PD [15].

Associations of Ccnb1 with chemical compounds

  • Western blot showed loss of nuclear as well as cytoplasmic cyclin A and cyclin B protein after 2-AAF treatment, while the Rb protein level was markedly increased during G1 [16].
  • Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions [17].
  • In addition, angiotensin II infusion dramatically increased Cks1 protein levels at capacitance arteries of normotensive rats, and angiotensin II treatment of isolated VSMC abrogated their ability to down-regulate Cks1 and maintain cyclin B protein expression in response to colcemid [3].
  • Olomoucine, a 2,6,9-trisubstituted purine, has been optimized for activity against CDK1/cyclin B by combinatorial and medicinal chemistry efforts to yield the purvalanol inhibitors [18].
  • To examine the therapeutic utility of this method, we transferred antisense phosphorothioate oligos against cyclin B1- and CDC2 kinase-encoding genes into balloon-injured rat carotid artery as a potential therapy for experimental restenosis [19].

Physical interactions of Ccnb1


Other interactions of Ccnb1


Analytical, diagnostic and therapeutic context of Ccnb1

  • We have cloned a rat cyclin B complementary DNA (cDNA) and have investigated cyclin B mRNA expression and regulation in the regenerating rat liver following 70% partial hepatectomy (PH) [25].
  • Western and Northern blot hybridization showed an increased expression of both cyclin D1 and its associated kinase cdk4, and cyclin B1 and its associated kinase cdc2, in livers of rats administered MY and MG after administration of DEN as compared to untreated or DEN controls [26].
  • These results demonstrate that: (i) the HVJ-liposome method enhances the half life and nuclear localization of antisense oligos in the vessel wall in vivo; and (ii) HVJ-mediated administration of antisense CDC2 kinase and cyclin B1 oligos produces a sustained inhibition of neointima formation after balloon angioplasty [19].
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) using specific cyclin B and D3 primers revealed that cyclins B and D3 originated from cardiomyocytes and noncardiomyocytes [27].


  1. Allelic imbalance and altered expression of genes in chromosome 2q11-2q16 from rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Qiu, C., Yu, M., Shan, L., Snyderwine, E.G. Oncogene (2003) [Pubmed]
  2. DNA fragmentation precedes aberrant expression of cell cycle-related protein in rat brain after MCA occlusion. Hayashi, T., Sakurai, M., Abe, K., Itoyama, Y. Neurol. Res. (1999) [Pubmed]
  3. Cks1 mediates vascular smooth muscle cell polyploidization. Hixon, M.L., Obejero-Paz, C., Muro-Cacho, C., Wagner, M.W., Millie, E., Nagy, J., Hassold, T.J., Gualberto, A. J. Biol. Chem. (2000) [Pubmed]
  4. Effects of diabetes and difluoromethylornithine treatment on hyperplasia, activity of MAP-kinase, and activity and association with cyclin B of p34cdc2 kinase in rat jejunal mucosa. Parekh, V.V., Hoffman, J.L., Younoszai, M.K. J. Investig. Med. (1998) [Pubmed]
  5. Microinjection of p34cdc2 kinase induces marked changes in cell shape, cytoskeletal organization, and chromatin structure in mammalian fibroblasts. Lamb, N.J., Fernandez, A., Watrin, A., Labbé, J.C., Cavadore, J.C. Cell (1990) [Pubmed]
  6. Emi1 is required for cytostatic factor arrest in vertebrate eggs. Reimann, J.D., Jackson, P.K. Nature (2002) [Pubmed]
  7. E2Fs link the control of G1/S and G2/M transcription. Zhu, W., Giangrande, P.H., Nevins, J.R. EMBO J. (2004) [Pubmed]
  8. CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo. Wheatley, S.P., Hinchcliffe, E.H., Glotzer, M., Hyman, A.A., Sluder, G., Wang, Y. J. Cell Biol. (1997) [Pubmed]
  9. The effects of radiation on the expression of a newly cloned and characterized rat cyclin B mRNA. Markiewicz, D.A., McKenna, W.G., Flick, M.B., Maity, A., Muschel, R.J. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
  10. Selective degradation of cyclin B1 mRNA in rat oocytes by RNA interference (RNAi). Lazar, S., Gershon, E., Dekel, N. J. Mol. Endocrinol. (2004) [Pubmed]
  11. Insulin-like growth factor-1 receptor and its ligand regulate the reentry of adult ventricular myocytes into the cell cycle. Reiss, K., Cheng, W., Pierzchalski, P., Kodali, S., Li, B., Wang, S., Liu, Y., Anversa, P. Exp. Cell Res. (1997) [Pubmed]
  12. Mediators of estradiol-stimulated mitosis in the rat uterine luminal epithelium. Zhang, Z., Laping, J., Glasser, S., Day, P., Mulholland, J. Endocrinology (1998) [Pubmed]
  13. 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]
  14. Coupling of epidermal growth factor (EGF) with the antiproliferative activity of cAMP induces neuronal differentiation. Mark, M.D., Storm, D.R. J. Biol. Chem. (1997) [Pubmed]
  15. Cell cycle aberrations by alpha-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. Lee, S.S., Kim, Y.M., Junn, E., Lee, G., Park, K.H., Tanaka, M., Ronchetti, R.D., Quezado, M.M., Mouradian, M.M. Neurobiol. Aging (2003) [Pubmed]
  16. Mitoinhibitory effects of the tumor promoter 2-acetylaminofluorene in rat liver: loss of E2F-1 and E2F-3 expression and cdk 2 kinase activity in late G1. Ohlson, L.C., Koroxenidou, L., Porsch-Hällström, I. J. Hepatol. (2004) [Pubmed]
  17. Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions. Malathi, K., Li, X., Krizanova, O., Ondrias, K., Sperber, K., Ablamunits, V., Jayaraman, T. J. Immunol. (2005) [Pubmed]
  18. Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. Knockaert, M., Gray, N., Damiens, E., Chang, Y.T., Grellier, P., Grant, K., Fergusson, D., Mottram, J., Soete, M., Dubremetz, J.F., Le Roch, K., Doerig, C., Schultz, P., Meijer, L. Chem. Biol. (2000) [Pubmed]
  19. Pharmacokinetics of antisense oligodeoxyribonucleotides (cyclin B1 and CDC 2 kinase) in the vessel wall in vivo: enhanced therapeutic utility for restenosis by HVJ-liposome delivery. Morishita, R., Gibbons, G.H., Kaneda, Y., Ogihara, T., Dzau, V.J. Gene (1994) [Pubmed]
  20. Differential regulation of cyclin B1 RNA and protein expression during hepatocyte growth in vivo. Trembley, J.H., Ebbert, J.O., Kren, B.T., Steer, C.J. Cell Growth Differ. (1996) [Pubmed]
  21. 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]
  22. Expression of cell cycle-related genes in dying cells in retinal ischemic injury. Kuroiwa, S., Katai, N., Shibuki, H., Kurokawa, T., Umihira, J., Nikaido, T., Kametani, K., Yoshimura, N. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  23. Gender-related differences in basal and hypoxia-induced activation of signal transduction pathways controlling cell cycle progression and apoptosis, in cardiac fibroblasts. Zhao, X., Eghbali-Webb, M. Endocrine (2002) [Pubmed]
  24. Cdc2-mediated phosphorylation of the gap junction protein, connexin43, during mitosis. Kanemitsu, M.Y., Jiang, W., Eckhart, W. Cell Growth Differ. (1998) [Pubmed]
  25. Posttranscriptional regulation of cyclin B messenger RNA expression in the regenerating rat liver. Trembley, J.H., Kren, B.T., Steer, C.J. Cell Growth Differ. (1994) [Pubmed]
  26. Tumor promotion by metanil yellow and malachite green during rat hepatocarcinogenesis is associated with dysregulated expression of cell cycle regulatory proteins. Gupta, S., Sundarrajan, M., Rao, K.V. Teratog., Carcinog. Mutagen. (2003) [Pubmed]
  27. Cyclins and cyclin dependent kinases during cardiac development. Kang, M.J., Kim, J.S., Chae, S.W., Koh, K.N., Koh, G.Y. Mol. Cells (1997) [Pubmed]
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