Cyclin B Family Proteins

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Cyclin B Family Proteins

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Cyclin B Family Proteins Background

Cyclin B is a key regulatory protein that controls mitosis in all eukaryotes, where it binds to the cyclin-dependent kinase cdk1 to form a complex that initiates the mitotic process by phosphorylation of selectins. Cyclin B regulates cdk1 activation, subcellular localization and substrate specificity, and disruption of cyclin B is essential for mitotic withdrawal. Overexpression of human cyclin B1 is found in a variety of cancers and is associated with tumor invasiveness. Here, we report that the crystal structure of human cyclin B1 reaches 2.9 Å. Comparison with the structure of cyclin A and cyclin E indicated that the N-terminal cyclin cassette motifs were very similar, but there was a significant difference between the C-terminal cyclin cassette leaves. Examination of the structure provides insight into the molecular basis of protein-based cyclin/affinity. Cdk inhibitors, such as p27, substrate recognition and cdk interactions.

 Structure of human cyclin B. Figure 1. Structure of human cyclin B.

Factors controlling cyclin B expression

1. Factors that regulate mitotic B-type cyclin genes in yeast

In S. cerevisiae, four type B cyclins with mitogenic functions have been identified, namely CLB1, CLB2, CLB3 and CLB4. CLB1 and CLB2 are closely related to each other and are closely related to cdc13, a type B cyclin that is critical for mitosis of S. pombe. In contrast to the increased CLB3 and CLB4 transcripts in the early S phase, CLB1 and CLB2 transcripts began to accumulate in the late S phase and remained elevated until the late mitosis. This expression pattern of CLB1 and CLB2 in the cell cycle is similar to the G2/M-specific expression of the animal cyclin B gene, so one can think that CLB1 and CLB2 are most relevant to animal cyclin B. Since the CLB2 promoter-lacZ fusion gene is regulated in a manner different from that of the endogenous CLB2 gene, changes in cell cycle regulation at the CLB2 transcript level are controlled at the transcriptional level.

2. Factors that regulate mitotic B-type cyclin genes in animals

The human type B cyclin is composed of three closely related members: cyclins B1, B2 and B3, which control the G2/M transition by interacting with the Cdc2 protein kinase. Cyclin B1 is the first human cyclin to be identified, with the best characteristics among the three members. Activation of Cdc2 kinase occurs only when sufficient cyclin B1 protein has been synthesized. The synthesis of the cyclin B1 protein (as with other types of cyclins) is associated with mRNA accumulation. Human cyclin B1 mRNA appeared at the end of S phase and reached peak expression in G2 and M phases. Cyclin B1-dependent cell cycle expression is critical for the right timing to enter mitosis. It has been suggested that unplanned expression of cyclins in tumor cells may result in abnormal regulation of the cell cycle.

Protein structure of Cdc2 kinaseFigure 2. Protein structure of Cdc2 kinase

Cyclin B1

Cyclin B1 is a regulatory protein involved in mitosis. Cyclin B1 determines whether cells participate in mitosis, thereby promoting the behavior of all or all of the switches. Its activation is well regulated and the positive feedback loop ensures that once the cyclin B1-Cdk1 complex is activated, it will not be inactivated. Cyclin B1-Cdk1 is involved in early events of mitosis, such as chromosome condensation, nuclear membrane rupture, and spindle assembly. Upon activation, cyclin B1-Cdk1 promotes a variety of early mitotic events. The active complex phosphorylates and activates the 13S cluster protein, which helps to agglomerate chromosomes. Another important function of the cyclin B1-Cdk1 complex is the destruction of the nuclear membrane. The nuclear membrane is a membrane structure that contains large protein complexes supported by the laminin network. Phosphorylation of lamins by cyclin B1-Cdk1 dissociates them, destroying the structural integrity of the nuclear membrane and causing it to rupture. The destruction of the nuclear envelope is important because it allows the mitotic spindle to enter the chromosome.

Structure of human cyclin B1.Figure 3. Structure of human cyclin B1.

Cyclin B2

Cyclin B2 is a member of the cyclin family, particularly the type B cyclin. B-type cyclins B1 and B2 are associated with p34cdc2 and are an important component of the cell cycle regulation mechanism. The subcellular localization of B1 and B2 is different. Cyclin B1 colocalizes with microtubules, while cyclin B2 is primarily associated with the Golgi region. Cyclin B2 also binds to transforming growth factor βRII, so cyclin B2/cdc2 may play a key role in TGF-mediated cell cycle control.

References:

1. Hershko A. et al. Mechanisms and regulation of the degradation of cyclin B. Cell Cycle. Trans. R. Soc. Lond. B Biol. Sci. 1999,354 (1389): 1571–5.

2. Petri, E.T.; et al. The crystal structure of human cyclin B. Cell Cycle. 2007,6 (11): 1342–9.

3. Masaki Ito.; et al. Factors controlling cyclin B expression. Plant Molecular Biology.2000, 43: 677–690, 2000.

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