Disease relevance of CCNB2

• In a series of 38 primary colorectal cancers, we detected in five tumors (13%) an accumulation of cyclin B1, which was neither related to mRNA overexpression nor to mutation within the coding region, and in five other tumors (13%) a 2-10-fold increase of cyclin B2 mRNA which was not related to gene amplification [1].
• In 94.7% of the samples this quotient correctly distinguished non-small cell lung cancer from normal lung tissue, suggesting the RAGE/cyclin-B2 quotient as a potential means for diagnosis of lung cancer [2].
• A dominant-negative form of NF-YA effectively inhibited the cyclin B2 promoter activity, and NF-Y was found to bind three conserved CCAAT boxes in the cyclin B2 promoter in colorectal adenocarcinoma cells [3].

High impact information on CCNB2

• Equally, directing cyclin B2 to the cytoplasm with the NH(2) terminus of cyclin B1 confers the broader properties of cyclin B1 [4].
• Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm [5].
• Thus, N-terminal fragments of cyclin A containing little more than the destruction box and its surroundings are indestructible. p34cdc2 binding also appears to be required for the destruction of cyclin B2 [6].
• We show that the expression of cyclin B1 overlaps the expression of cyclin B2 in the mature testis, but not vice versa [7].
• Cyclin B1 can be found both on intracellular membranes and free in the cytoplasm, in contrast to cyclin B2, which is membrane-associated [7].

Biological context of CCNB2

• In contrast to cyclin B1, cyclin B2 does not relocate to the nucleus at prophase, but becomes uniformly distributed throughout the cell [8].
• Both male and female cyclin B2-null mice were fertile, which was unexpected in view of the high levels and distinct patterns of expression of cyclin B2 during spermatogenesis [7].
• Together with the recently described mouse cdc25C promoter, human cyclin B2 is the second identified gene which solely requires a CHR for its cell cycle regulation [9].
• Phosphopeptide analysis identified Ser53 as the major in vitro phosphorylation site for cyk in cyclin B2 [10].
• At first, protein levels of both cyclin Bs were examined by immunoblotting, revealing that immature oocytes had only CB2, at a level comparable to 1/20 to 1/40 of that detected in first metaphase oocytes [11].

Anatomical context of CCNB2

• Cyclin B1 co-localizes with microtubules, whereas cyclin B2 is primarily associated with the Golgi region [8].
• Characterization and physiological importance of a novel cell cycle regulated protein kinase in Xenopus laevis oocytes that phosphorylates cyclin B2 [10].
• Expression of a non-destructible cyclin B2 mutant causes HeLa cells to arrest in mitosis [12].

Associations of CCNB2 with chemical compounds

• Utilizing the cytoplasmic tail of Transforming Growth Factor Receptor Type II (TGFbeta RII) as bait in a yeast two hybrid system, we have identified human cyclin B2 as a direct physical partner of TGFbeta RII [13].
• They contain a store of preMPF composed of tyrosine phosphorylated p34cdc2 and cyclin B2 [14].
• Using a synthetic peptide derived from cyclin B2 encompassing Ser53 (cyktide) as a substrate, cyk was shown to be activated during progesterone-induced maturation, with a peak of activity between 40 and 50% maturation [10].
• We have partially purified a specific cyclin B2 kinase (cyk) from prophase oocytes of Xenopus laevis after an ATP-gamma-S activation step [10].
• We show that upon treatment of HepG2 cells with 5-fluorouracil or methotrexate, p53 levels increase while concentrations of cyclin B2 mRNA, measured by RT-PCR with the LightCycler system, are reduced [15].

Physical interactions of CCNB2

• More importantly, TGFbeta RII co-precipitated with cyclin B2 in TGFbeta-treated THP-1 cells [13].

Other interactions of CCNB2

• CDC2 mRNA transcript levels correlated significantly with those of CCNB1 and CCNB2 mRNA [16].
• Conversely, of the 35 genes overexpressed in NEECs, three genes, STK15, BUB1, and CCNB2, are involved in the regulation of the mitotic spindle checkpoint [17].
• Using recombinant proteins, Cdc2 was demonstrated to indirectly interact with TGFbeta RII via cyclin B2 [13].
• This interaction was reproduced in THP-1 monocytic cells, where TGFbeta treatment markedly enhanced the ability of cyclin B2 and, correspondingly, Cdc2 from TGFbeta-treated THP-1 cells, to bind the GST-TGFbeta RII fusion protein [13].
• Brain-derived neurotrophic factor prevented both the increase of cyclin B2 expression in the G4-positive neurones and the NGF-induced cell death [18].

Analytical, diagnostic and therapeutic context of CCNB2

• NF-Y binding to the human cyclin B2 promoter could be shown by chromatin immunoprecipitation (ChIP) assays [9].
• We obtained a porcine CB2 cDNA fragment, which was 88% homologous with human CB2, by reverse-transcriptase polymerase chain reaction (RT-PCR) using total RNAs of immature porcine oocytes and a primer set of human CB2 [11].
• DNA microarray analysis of 99 lung tumor samples and 15 normal lung tissues revealed that receptor for advanced glycation end products (RAGE) mRNA is reduced fourfold (p = 7.8 x 10(-11)) and cyclin-B2 mRNA is upregulated twofold (p = 5.9 x 10(-18)) in lung carcinoma compared with normal lung [2].

References