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Gene Review

CCNB1  -  cyclin B1

Homo sapiens

Synonyms: CCNB, G2/mitotic-specific cyclin-B1
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Disease relevance of CCNB1


Psychiatry related information on CCNB1


High impact information on CCNB1


Chemical compound and disease context of CCNB1


Biological context of CCNB1

  • Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively [18].
  • In summary, these results suggest that stress-related effector genes are altered in cells after treatment with fractionated irradiation, and that up-regulation of CCNB1 is responsible, at least in part, for radioresistance after fractionated irradiation [19].
  • To determine if any of the changes in gene expression could be responsible for the induced radioresistance, CCNB1 and CDKN1A, both of which were up-regulated in MCF-IR20 cells and down-regulated in MCF-RV cells, were studied further by transfection with antisense oligonucleotides [19].
  • An anti-phospho-S147 antibody reacts specifically with cyclin B1 only during G2/M phase [20].
  • Phosphorylation of cyclin B1 is central to its nuclear translocation, but the kinases that are responsible remain unknown [20].

Anatomical context of CCNB1


Associations of CCNB1 with chemical compounds


Physical interactions of CCNB1

  • The best characterized of the cyclin-containing complexes is the association of cyclin B with the p34cdc2 kinase [27].
  • To address this question, chromatin containing prereplication complexes was driven into mitosis with Cdk1/cyclin B [28].
  • Phosphorylated p21 binds to cyclin B1 when Cdc2 is phosphorylated on Y15 and associates poorly with the complex [29].
  • No detectable phosphorylation of the p34 protein was observed with cdk2 complexed with either cyclin B1 or A [30].
  • We also find that wild-type, but not mutant, p53 protein binds Sp1 and the cyclin B1 promoter [31].

Enzymatic interactions of CCNB1


Regulatory relationships of CCNB1


Other interactions of CCNB1

  • In vertebrate cells, the nuclear entry of Cdc2-cyclin B1 (MPF) during prophase is thought to be essential for the induction and coordination of M-phase events [20].
  • The p34cdc2/cyclin B complex is required for the G2 to M transition (see refs 1-4 for review), but the physiological role of other cyclin complexes is unclear [27].
  • How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity remains unknown [39].
  • Cyclin A is degraded during metaphase and cyclin B1 is precipitously destroyed at the metaphase----anaphase transition [23].
  • Cyclin B1 co-localizes with microtubules, whereas cyclin B2 is primarily associated with the Golgi region [40].

Analytical, diagnostic and therapeutic context of CCNB1


  1. High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma. Björck, E., Ek, S., Landgren, O., Jerkeman, M., Ehinger, M., Björkholm, M., Borrebaeck, C.A., Porwit-MacDonald, A., Nordenskjöld, M. Blood (2005) [Pubmed]
  2. Human T-lymphotropic virus type 1 oncoprotein tax promotes unscheduled degradation of Pds1p/securin and Clb2p/cyclin B1 and causes chromosomal instability. Liu, B., Liang, M.H., Kuo, Y.L., Liao, W., Boros, I., Kleinberger, T., Blancato, J., Giam, C.Z. Mol. Cell. Biol. (2003) [Pubmed]
  3. T-loop deletion of CDC2 from breast cancer tissues eliminates binding to cyclin B1 and cyclin-dependent kinase inhibitor p21. Ohta, T., Okamoto, K., Isohashi, F., Shibata, K., Fukuda, M., Yamaguchi, S., Xiong, Y. Cancer Res. (1998) [Pubmed]
  4. Decrease in susceptibility toward induction of apoptosis and alteration in G1 checkpoint function as determinants of resistance of human lung cancer cells against the antisignaling drug UCN-01 (7-Hydroxystaurosporine). Sugiyama, K., Akiyama, T., Shimizu, M., Tamaoki, T., Courage, C., Gescher, A., Akinaga, S. Cancer Res. (1999) [Pubmed]
  5. Knockdown of MBP-1 in human prostate cancer cells delays cell cycle progression. Ghosh, A.K., Steele, R., Ray, R.B. J. Biol. Chem. (2006) [Pubmed]
  6. Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease. Zhu, X., McShea, A., Harris, P.L., Raina, A.K., Castellani, R.J., Funk, J.O., Shah, S., Atwood, C., Bowen, R., Bowser, R., Morelli, L., Perry, G., Smith, M.A. J. Neurosci. Res. (2004) [Pubmed]
  7. Cell cycle markers in the hippocampus in Alzheimer's disease. Nagy, Z., Esiri, M.M., Cato, A.M., Smith, A.D. Acta Neuropathol. (1997) [Pubmed]
  8. Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. Bhat, M.A., Philp, A.V., Glover, D.M., Bellen, H.J. Cell (1996) [Pubmed]
  9. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Blangy, A., Lane, H.A., d'Hérin, P., Harper, M., Kress, M., Nigg, E.A. Cell (1995) [Pubmed]
  10. Functional analysis of the P box, a domain in cyclin B required for the activation of Cdc25. Zheng, X.F., Ruderman, J.V. Cell (1993) [Pubmed]
  11. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Girard, F., Strausfeld, U., Fernandez, A., Lamb, N.J. Cell (1991) [Pubmed]
  12. A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Ghiara, J.B., Richardson, H.E., Sugimoto, K., Henze, M., Lew, D.J., Wittenberg, C., Reed, S.I. Cell (1991) [Pubmed]
  13. Genistein-induced G2/M arrest is associated with the inhibition of cyclin B1 and the induction of p21 in human breast carcinoma cells. Choi, Y.H., Zhang, L., Lee, W.H., Park, K.Y. Int. J. Oncol. (1998) [Pubmed]
  14. Prominent induction of cyclin B1 in G2/M renal cancer cells with butyrolactone 1. Kasuya, Y., Hosaka, Y., Matsushima, H., Goto, T., Kitamura, T., Okuyama, A. International journal of urology : official journal of the Japanese Urological Association. (2003) [Pubmed]
  15. Regulation of cyclin B1 by estradiol and polyamines in MCF-7 breast cancer cells. Thomas, T., Thomas, T.J. Cancer Res. (1994) [Pubmed]
  16. Repression of cyclin B1 expression after treatment with adriamycin, but not cisplatin in human lung cancer A549 cells. Dan, S., Yamori, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  17. Inhibition of mitotic cyclin B and cdc2 kinase activity by selenomethionine in synchronized colon cancer cells. Chigbrow, M., Nelson, M. Anticancer Drugs (2001) [Pubmed]
  18. Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively. Sartor, H., Ehlert, F., Grzeschik, K.H., Müller, R., Adolph, S. Genomics (1992) [Pubmed]
  19. Effector genes altered in MCF-7 human breast cancer cells after exposure to fractionated ionizing radiation. Li, Z., Xia, L., Lee, L.M., Khaletskiy, A., Wang, J., Wong, J.Y., Li, J.J. Radiat. Res. (2001) [Pubmed]
  20. Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase. Toyoshima-Morimoto, F., Taniguchi, E., Shinya, N., Iwamatsu, A., Nishida, E. Nature (2001) [Pubmed]
  21. Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. Ookata, K., Hisanaga, S., Bulinski, J.C., Murofushi, H., Aizawa, H., Itoh, T.J., Hotani, H., Okumura, E., Tachibana, K., Kishimoto, T. J. Cell Biol. (1995) [Pubmed]
  22. Mitotic regulation of the human anaphase-promoting complex by phosphorylation. Kraft, C., Herzog, F., Gieffers, C., Mechtler, K., Hagting, A., Pines, J., Peters, J.M. EMBO J. (2003) [Pubmed]
  23. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. Pines, J., Hunter, T. J. Cell Biol. (1991) [Pubmed]
  24. A direct role for GRASP65 as a mitotically regulated Golgi stacking factor. Wang, Y., Seemann, J., Pypaert, M., Shorter, J., Warren, G. EMBO J. (2003) [Pubmed]
  25. Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1. Moore, J.D., Yang, J., Truant, R., Kornbluth, S. J. Cell Biol. (1999) [Pubmed]
  26. The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Liu, F., Stanton, J.J., Wu, Z., Piwnica-Worms, H. Mol. Cell. Biol. (1997) [Pubmed]
  27. Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Tsai, L.H., Harlow, E., Meyerson, M. Nature (1991) [Pubmed]
  28. DNA replication of mitotic chromatin in Xenopus egg extracts. Prokhorova, T.A., Mowrer, K., Gilbert, C.H., Walter, J.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Phosphorylation of p21 in G2/M promotes cyclin B-Cdc2 kinase activity. Dash, B.C., El-Deiry, W.S. Mol. Cell. Biol. (2005) [Pubmed]
  30. Characterization of the in vitro reconstituted cyclin A or B1-dependent cdk2 and cdc2 kinase activities. Pan, Z.Q., Amin, A., Hurwitz, J. J. Biol. Chem. (1993) [Pubmed]
  31. p53 is a NF-Y- and p21-independent, Sp1-dependent repressor of cyclin B1 transcription. Innocente, S.A., Lee, J.M. FEBS Lett. (2005) [Pubmed]
  32. Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells. Barth, H., Klingler, M., Aktories, K., Kinzel, V. Infect. Immun. (1999) [Pubmed]
  33. Cdc2-cyclin B phosphorylates p70 S6 kinase on Ser411 at mitosis. Papst, P.J., Sugiyama, H., Nagasawa, M., Lucas, J.J., Maller, J.L., Terada, N. J. Biol. Chem. (1998) [Pubmed]
  34. The protein kinase C inhibitor ilmofosine (BM 41 440) arrests cells in G2 phase and suppresses CDC2 kinase activation through a mechanism different from that of DNA damaging agents. Hofmann, J., O'Connor, P.M., Jackman, J., Schubert, C., Ueberall, F., Kohn, K.W., Grunicke, H. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  35. Multisite phosphorylation of nuclear interaction partner of ALK (NIPA) at G2/M involves cyclin B1/Cdk1. Bassermann, F., von Klitzing, C., Illert, A.L., Münch, S., Morris, S.W., Pagano, M., Peschel, C., Duyster, J. J. Biol. Chem. (2007) [Pubmed]
  36. p53 regulates a G2 checkpoint through cyclin B1. Innocente, S.A., Abrahamson, J.L., Cogswell, J.P., Lee, J.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  37. Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes. Liu, F., Rothblum-Oviatt, C., Ryan, C.E., Piwnica-Worms, H. Mol. Cell. Biol. (1999) [Pubmed]
  38. Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro. Connell-Crowley, L., Solomon, M.J., Wei, N., Harper, J.W. Mol. Biol. Cell (1993) [Pubmed]
  39. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Lukas, C., Sørensen, C.S., Kramer, E., Santoni-Rugiu, E., Lindeneg, C., Peters, J.M., Bartek, J., Lukas, J. Nature (1999) [Pubmed]
  40. Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus. Jackman, M., Firth, M., Pines, J. EMBO J. (1995) [Pubmed]
  41. Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line. Abal, M., Bras-Goncalves, R., Judde, J.G., Fsihi, H., De Cremoux, P., Louvard, D., Magdelenat, H., Robine, S., Poupon, M.F. Oncogene (2004) [Pubmed]
  42. Varicella-zoster virus infection of human foreskin fibroblast cells results in atypical cyclin expression and cyclin-dependent kinase activity. Leisenfelder, S.A., Moffat, J.F. J. Virol. (2006) [Pubmed]
  43. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Joe, A.K., Liu, H., Suzui, M., Vural, M.E., Xiao, D., Weinstein, I.B. Clin. Cancer Res. (2002) [Pubmed]
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