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

• Because Ca(2+) spiking was not inhibited by Delta 90 cyclin B1, the degradation timing of securin, visualized by coupling it to EGFP, was unaffected [18].
• The release of HeLa cells from metaphase arrest in the presence of exogenous H(2)O(2) inhibited the ubiquitination of cyclin B1 as well as the degradation of cyclin B1 and securin that were apparent in the absence of H(2)O(2) [19].
• Furthermore, there might exist signaling cascade such as PKC activation and cyclin B down-regulation after 8-Cl-cAMP and 8-Cl-adenosine treatment [20].
• In contrast to the G1 arrest, adriamycin-induced G2 arrest was relatively tight and correlated with the Thr-14/Tyr-15 phosphorylation of cyclin B-Cdc2 complexes [21].
• Moreover, treatment with butyrolactone I, a specific inhibitor of Cdc2 kinase, inhibits nuclear translocation of cyclin B1 in those embryos [22].

Physical interactions of Ccnb1

• Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation [23].
• These data would suggest that delaying the onset of M phase in NIH 3T3 cells in which the rate of DNA replication is reduced, is first ensured by a mechanism that prevents the cytoplasmic relocation of inactive p34cdc2/cyclin B1 complexes continually forming in the nucleus once the G1 period of mitotic cyclin instability is over [24].

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

• In conclusion, our results suggest that the UPP plays important roles in oocyte meiosis resumption, spindle assembly, polar body emission, and pronuclear formation, probably by regulating cyclin B1 degradation and MAPK/p90rsk phosphorylation [28].
• In addition, cyclin B1, cyclin D, and cyclin E were overexpressed in intestinal cells after fast-neutron irradiation and their immunoreactivities were increased strongly in round and oval cells of laminar propria in villi core and crypts [29].
• When UPP was inhibited, mitogen-activated protein kinase (MAPK)/p90rsk phosphorylation was not affected, but the cyclin B1 degradation that occurs during normal metaphase-anaphase transition was not observed [28].
• Cyclin B consistently demonstrated a pattern opposite to a somatic G2/M cyclin, with peak levels in G1 declining through S phase to a low in G2 during each of the three cell cycles examined [30].
• Morphogenesis analysis such as microtubule stabilization, Wee1 distribution, and cyclin B location were observed by immunofluorescence confocal microscopy [31].

Analytical, diagnostic and therapeutic context of Ccnb1

• Western immunoblotting revealed elevated expression of the mitotic effector molecules, cyclin A, cyclin B1 and cdc20 in IgHmu-HOX11(Tg) cultures [32].
• PKI microinjection also prevented cyclin B degradation and sustained MPF activity, thus delaying the transition from metaphase to anaphase [33].
• Through Southern blot analyses of DNA from backcross and cogenic mice, recombinant inbred strains, and somatic cell hybrids, the genetic loci that produce the cyclin B1-related sequences (designated loci Cycb1-rs1 to Cycb1-rs9) were mapped on mouse chromosomes 5, 1, 17, 4, 14, 13, 7, X, and 8, respectively [34].
• In the normal lens, our experiments using in-situ hybridization reveal that the expression of cyclin A, cyclin B1, cdc2 and cdk2 is restricted to the proliferative epithelial cells, with no expression in the differentiating fiber cells [35].
• To explore the mechanism by which PMA potentiates polyploidization, the levels of the G1 checkpoint-related proteins cyclin E and cdk2, and those of the G2 checkpoint-related proteins cyclin B and cdc2 were determined by flow cytometry [36].

References