Cyclin B1

2B9R, 2JGZ, 4Y72, 5HQ0, 4YC3891434175ENSG00000134057n/aP14635n/aNM_031966NM_001354844NM_001354845n/aNP_114172NP_001341773NP_001341774n/aG2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene.2b9r: Crystal Structure of Human Cyclin B12jgz: CRYSTAL STRUCTURE OF PHOSPHO-CDK2 IN COMPLEX WITH CYCLIN B G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene. Cyclin B1 is a regulatory protein involved in mitosis. The gene product complexes with p34 (Cdk1) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript that is expressed predominantly during G2/M phase of the cell cycle. The different transcripts result from the use of alternate transcription initiation sites. Cyclin B1 contributes to the switch-like all or none behavior of the cell in deciding to commit to mitosis. Its activation is well-regulated, and positive feedback loops ensure that once the cyclin B1-Cdk1 complex is activated, it is not deactivated. Cyclin B1-Cdk1 is involved in the early events of mitosis, such as chromosome condensation, nuclear envelope breakdown, and spindle pole assembly. Once activated, cyclin B1-Cdk1 promotes several of the events of early mitosis. The active complex phosphorylates and activates 13S condensin, which helps to condense chromosomes. Another important function of the cyclin B1-Cdk1 complex is to break down the nuclear envelope. The nuclear envelope is a membranous structure containing large protein complexes supported by a network of nuclear lamins. Phosphorylation of the lamins by cyclin B1-Cdk1 causes them to dissociate, compromising the structural integrity of the nuclear envelope so that it breaks down. The destruction of the nuclear envelope is important because it allows the mitotic spindle to access the chromosomes. Like all cyclins, levels of cyclin B1 oscillate over the course of the cell cycle. Just prior to mitosis, a large amount of cyclin B1 is present in the cell, but it is inactive due to phosphorylation of Cdk1 by the Wee1 kinase. The complex is activated by dephosphorylation by the phosphatase Cdc25. Cdc25 is always present in the cell but must be activated by phosphorylation. A possible trigger for activation is phosphorylation by cyclin A-Cdk, which functions before cyclin B1-Cdk in the cell cycle. Active Cdk1 is also capable of phosphorylating and activating Cdc25 and thus promote its own activation, resulting in a positive feedback loop. Once cyclin B1-Cdk1 is activated, it remains stably active for the rest of mitosis. Another mechanism by which cyclin B1-Cdk1 activity is regulated is through subcellular localization. Before mitosis almost all cyclin B1 in the cell is located in the cytoplasm, but in late prophase it relocates to the nucleus. This is regulated by the phosphorylation of cyclin B1, in contrast to phosphorylation of Cdk1 regulating the activity of the complex. Phosphorylation of cyclin B1 causes it to be imported to the nucleus, and phosphorylation also prevents export from the nucleus by blocking the nuclear export signal. Cyclin B1 is phosphorylated by Polo kinase and Cdk1, again setting up a positive feedback loop that commits cyclin B1-Cdk1 to its fate. At the end of mitosis, cyclin B1 is targeted for degradation by the APC through its APC localization sequence, permitting the cell to exit mitosis. Cyclin B1 has been shown to interact with Cdk1,