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Gene Review

Ccnb1  -  cyclin B1

Mus musculus

Synonyms: Ccn-2, Ccnb1-rs1, Ccnb1-rs13, CycB1, Cycb, ...
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Disease relevance of Ccnb1

  • Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins [1].
  • Furthermore, we found that Icat inhibits both dephosphorylation of Cdc2 and nuclear translocation of cyclin B1 and induces G(2) arrest followed by cell death in colorectal tumor cells [2].
  • The level of expression of cyclin B1 and p34cdc2 protein was decreased in the transplantable murine hepatoma 22 treated with resveratrol whereas the expression of cyclin D1 protein did not change [3].
  • AIM: To study the antitumour activity of resveratrol and its effect on the expression of cell cycle proteins including cyclin D1, cyclin B1 and p34cdc2 in transplanted liver cancer of murine [3].
  • In a two-hybrid screen using a bait protein to mimic phosphorylated cyclin B1, we identified a novel interaction between cyclin B1 and patched1 (ptc1), a tumor suppressor associated with basal cell carcinoma (BCC) [4].

High impact information on Ccnb1

  • Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded [5].
  • Cyclin A and cdk2, but not cyclin B1 and cdc2, were specifically localized at nuclear replication foci, just like the replication protein proliferating cell nuclear antigen [6].
  • We demonstrate that FKH-TFs regulate expression of mitotic genes such as cyclin B and polo-like kinase (Plk) [7].
  • These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry [8].
  • Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes [9].

Biological context of Ccnb1

  • Additionally, we have isolated the coding region of the mouse orthologue, Mrad17, and mapped it on chromosome 13 between Ccnb1 and Btf2p44, the same two genes between which it maps in human [10].
  • The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis [11].
  • Cyclin B1 proved to be an essential gene; no homozygous B1-null pups were born [12].
  • We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis [13].
  • In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention [13].

Anatomical context of Ccnb1

  • Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells [13].
  • In Northern analysis, two cyclin A-related transcripts of 2.1 and 3.4 kb and three cyclin B1-related transcripts of 1.7, 2.1, and 2.7 kb were detected in embryonic stem cells and postimplantation embryos from Day 9.5 to 15.5 of development [14].
  • TNF-alpha mRNA levels were significantly elevated in the hippocampus by 12 h and remained elevated for 72 h. mRNA levels for cyclin A2 and cyclin B1 were elevated by approximately 2-fold at 72 h [15].
  • Moreover, the significant reduction in hepatocyte mitosis was associated with diminished mRNA levels and nuclear expression of Cdc25B phosphatase and delayed accumulation of cyclin B1 protein, which is required for Cdk1 activation and entry into mitosis [16].
  • We found that cyclin B1 protein accumulates in the nucleus of cells that are sensitive to gamma radiation-induced apoptosis (thymocytes, lymphoid cell lines), but remains cytoplasmic in apoptosis-resistant cells (primary and transformed fibroblasts) [17].

Associations of Ccnb1 with chemical compounds


Physical interactions of Ccnb1


Regulatory relationships of Ccnb1

  • Cyclin B1 degradation reduces maturation (M-phase)-promoting factor (MPF) activity and securin degradation allows sister chromatid separation [18].
  • Besides, after 8-Cl-cAMP and 8-Cl-adenosine treatment, cyclin B was down-regulated and a CDK inhibitor, p27 was up-regulated in a time-dependent manner [20].
  • In the present study we blocked the function of Bub1 during meiosis by microinjecting anti-Bub1 specific antibody into cytoplasm of mouse oocytes, and found that depletion of Bub1 induced evident cyclin B degradation and precocious anaphase onset [25].
  • M-phase promoting factor is a complex of cdc2 and cyclin B that is regulated positively by cdc25 phosphatase and negatively by wee1 kinase [26].
  • This was correlated with a failure of the injected eggs to accumulate newly synthesized cyclin B. The c-mos protooncogene thus appears to affect the pathway that regulates cyclin B stability during meiosis of mouse eggs [27].

Other interactions of Ccnb1


Analytical, diagnostic and therapeutic context of Ccnb1


  1. CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability. Fraser, M.M., Watson, P.M., Fraig, M.M., Kelley, J.R., Nelson, P.S., Boylan, A.M., Cole, D.J., Watson, D.K. Cancer Res. (2005) [Pubmed]
  2. Overexpression of Icat induces G(2) arrest and cell death in tumor cell mutants for adenomatous polyposis coli, beta-catenin, or Axin. Sekiya, T., Nakamura, T., Kazuki, Y., Oshimura, M., Kohu, K., Tago, K., Ohwada, S., Akiyama, T. Cancer Res. (2002) [Pubmed]
  3. Effect of resveratrol on cell cycle proteins in murine transplantable liver cancer. Yu, L., Sun, Z.J., Wu, S.L., Pan, C.E. World J. Gastroenterol. (2003) [Pubmed]
  4. Patched1 interacts with cyclin B1 to regulate cell cycle progression. Barnes, E.A., Kong, M., Ollendorff, V., Donoghue, D.J. EMBO J. (2001) [Pubmed]
  5. Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Ayad, N.G., Rankin, S., Murakami, M., Jebanathirajah, J., Gygi, S., Kirschner, M.W. Cell (2003) [Pubmed]
  6. Reversal of terminal differentiation and control of DNA replication: cyclin A and Cdk2 specifically localize at subnuclear sites of DNA replication. Cardoso, M.C., Leonhardt, H., Nadal-Ginard, B. Cell (1993) [Pubmed]
  7. Forkhead transcription factors contribute to execution of the mitotic programme in mammals. Alvarez, B., Martínez-A, C., Burgering, B.M., Carrera, A.C. Nature (2001) [Pubmed]
  8. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Sanchez, Y., Wong, C., Thoma, R.S., Richman, R., Wu, Z., Piwnica-Worms, H., Elledge, S.J. Science (1997) [Pubmed]
  9. Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Homer, H.A., McDougall, A., Levasseur, M., Yallop, K., Murdoch, A.P., Herbert, M. Genes Dev. (2005) [Pubmed]
  10. Human and mouse RAD17 genes: identification, localization, genomic structure and histological expression pattern in normal testis and seminoma. von Deimling, F., Scharf, J.M., Liehr, T., Rothe, M., Kelter, A.R., Albers, P., Dietrich, W.F., Kunkel, L.M., Wernert, N., Wirth, B. Hum. Genet. (1999) [Pubmed]
  11. RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway. Suzumori, N., Burns, K.H., Yan, W., Matzuk, M.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero. Brandeis, M., Rosewell, I., Carrington, M., Crompton, T., Jacobs, M.A., Kirk, J., Gannon, J., Hunt, T. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo. Yuan, J., Krämer, A., Matthess, Y., Yan, R., Spänkuch, B., Gätje, R., Knecht, R., Kaufmann, M., Strebhardt, K. Oncogene (2006) [Pubmed]
  14. A single cyclin A gene and multiple cyclin B1-related sequences are dispersed in the mouse genome. Lock, L.F., Pines, J., Hunter, T., Gilbert, D.J., Gopalan, G., Jenkins, N.A., Copeland, N.G., Donovan, P.J. Genomics (1992) [Pubmed]
  15. Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage. McPherson, C.A., Kubik, J., Wine, R.N., D'Hellencourt, C.L., Harry, G.J. Neurotoxicity research. (2003) [Pubmed]
  16. The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration. Wang, X., Kiyokawa, H., Dennewitz, M.B., Costa, R.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. Nuclear localization of cyclin B1 regulates DNA damage-induced apoptosis. Porter, L.A., Cukier, I.H., Lee, J.M. Blood (2003) [Pubmed]
  18. Maintenance of sister chromatid attachment in mouse eggs through maturation-promoting factor activity. Madgwick, S., Nixon, V.L., Chang, H.Y., Herbert, M., Levasseur, M., Jones, K.T. Dev. Biol. (2004) [Pubmed]
  19. The RING-H2-finger protein APC11 as a target of hydrogen peroxide. Chang, T.S., Jeong, W., Lee, D.Y., Cho, C.S., Rhee, S.G. Free Radic. Biol. Med. (2004) [Pubmed]
  20. 8-Cl-cAMP and its metabolite, 8-Cl-adenosine induce growth inhibition in mouse fibroblast DT cells through the same pathways: protein kinase C activation and cyclin B down-regulation. Ahn, Y.H., Jung, J.M., Hong, S.H. J. Cell. Physiol. (2004) [Pubmed]
  21. G1 versus G2 cell cycle arrest after adriamycin-induced damage in mouse Swiss3T3 cells. Siu, W.Y., Yam, C.H., Poon, R.Y. FEBS Lett. (1999) [Pubmed]
  22. Nuclear accumulation of cyclin B1 in mouse two-cell embryos is controlled by the activation of Cdc2. Ohashi, A., Minami, N., Imai, H. Biol. Reprod. (2001) [Pubmed]
  23. Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation. Nandan, M.O., Chanchevalap, S., Dalton, W.B., Yang, V.W. FEBS Lett. (2005) [Pubmed]
  24. Delaying the onset of M phase in NIH 3T3 cells blocked in early S phase occurs via accumulating cyclin B1 and tyrosine-phosphorylated p34cdc2 in the nucleus. David-Pfeuty, T., Nouvian-Dooghe, Y., Rouillard, D. Biol. Cell (1997) [Pubmed]
  25. Bub1 prevents chromosome misalignment and precocious anaphase during mouse oocyte meiosis. Yin, S., Wang, Q., Liu, J.H., Ai, J.S., Liang, C.G., Hou, Y., Chen, D.Y., Schatten, H., Sun, Q.Y. Cell Cycle (2006) [Pubmed]
  26. c-Fos/activator protein-1 transactivates wee1 kinase at G(1)/S to inhibit premature mitosis in antigen-specific Th1 cells. Kawasaki, H., Komai, K., Ouyang, Z., Murata, M., Hikasa, M., Ohgiri, M., Shiozawa, S. EMBO J. (2001) [Pubmed]
  27. The c-mos gene product is required for cyclin B accumulation during meiosis of mouse eggs. O'Keefe, S.J., Kiessling, A.A., Cooper, G.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  28. Ubiquitin-proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation. Huo, L.J., Fan, H.Y., Zhong, Z.S., Chen, D.Y., Schatten, H., Sun, Q.Y. Mech. Dev. (2004) [Pubmed]
  29. p53 and cell-cycle-regulated protein expression in small intestinal cells after fast-neutron irradiation in mice. Jee, Y.H., Jeong, W.I., Kim, T.H., Hwang, I.S., Ahn, M.J., Joo, H.G., Hong, S.H., Jeong, K.S. Mol. Cell. Biochem. (2005) [Pubmed]
  30. Patterns of expression of cyclins A, B1, D, E and cdk 2 in preimplantation mouse embryos. Waclaw, R.R., Chatot, C.L. Zygote (2004) [Pubmed]
  31. Cell cycle regulation by the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line. Hashimoto, O., Shinkawa, M., Torimura, T., Nakamura, T., Selvendiran, K., Sakamoto, M., Koga, H., Ueno, T., Sata, M. BMC Cancer (2006) [Pubmed]
  32. Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice. Chen, E., Lim, M.S., Rosic-Kablar, S., Liu, J., Jolicoeur, P., Dubé, I.D., Hough, M.R. Oncogene (2006) [Pubmed]
  33. Protein kinase A regulates cell cycle progression of mouse fertilized eggs by means of MPF. Yu, B., Wang, Y., Liu, Y., Liu, Y., Li, X., Wu, D., Zong, Z., Zhang, J., Yu, D. Dev. Dyn. (2005) [Pubmed]
  34. Expression of murine cyclin B1 mRNAs and genetic mapping of related genomic sequences. Hanley-Hyde, J., Mushinski, J.F., Sadofsky, M., Huppi, K., Krall, M., Kozak, C.A., Mock, B. Genomics (1992) [Pubmed]
  35. Regulation of cyclin and cyclin-dependent kinase gene expression during lens differentiation requires the retinoblastoma protein. Fromm, L., Overbeek, P.A. Oncogene (1996) [Pubmed]
  36. Involvement of protein kinase C in taxol-induced polyploidization in a cultured sarcoma cell line. Zong, Z.P., Fujikawa-Yamamoto, K., Li, A.L., Yamaguchi, N., Chang, Y.G., Murakami, M., Ishikawa, Y. Eur. J. Pharmacol. (2000) [Pubmed]
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