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. Interactions Cyclin B1 has been shown to interact with Cdk1, GADD45A and RALBP1. Cancer One of the hallmarks of cancer is the lack of regulation in the cell cycle. The role of cyclin B1 is to transition the cell from G2 to M phase but becomes unregulated in cancer cells where overexpression of cyclin B1 can lead to uncontrolled cell growth by binding to its partner Cdks. Binding of Cdks can lead to phosphorylation of other substrates at inappropriate time and unregulated proliferation. This is a consequence of p53, tumor suppressor protein, being inactivated. Wild-type p53 have been shown to suppress cyclin B1 expression. Previous work has shown that high cyclin B1 expression levels are found in variety of cancers such as breast, cervical, gastric, colorectal, head and neck squamous cell, non-small-cell lung cancer, colon, prostate, oral and esophageal. High expression levels are usually seen before the tumor cells become immortalized and aneuploid which can contribute to the chromosomal instability and the aggressive nature of certain cancers. These high levels of cyclin B1 can also be associated to the extent of tumor invasion and aggressiveness therefore concentration of cyclin B1 can be used to determine the prognosis of cancer patients. For example, an increase in expression of cyclin B1/cdc2 is significantly higher in breast tumor tissue and shown to increase lymph node metastasis in breast cancer. Cyclin B1 can reside in the nucleus or the cytoplasm which can have an effect on the malignant potential of cyclin B1 when overexpressed in each location. Nuclear-dominant expression of cyclin B1 leads to poorer prognosis due to its weak activity compared to cytoplasmic cyclin B1. This trend has been observed in esophageal cancer, head and neck squamous cell cancer and breast cancer. Down regulation and tumor suppression While the exact mechanism that explains how cyclin B1 becomes overexpressed is not very well understood, previous