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  • Title: The Plk1 Polo box domain mediates a cell cycle and DNA damage regulated interaction with Chk2.
    Author: Tsvetkov LM, Tsekova RT, Xu X, Stern DF.
    Journal: Cell Cycle; 2005 Apr; 4(4):609-17. PubMed ID: 15876876.
    Abstract:
    Polo-like kinase 1 (Plk1) regulates multiple processes during mitosis. Chk2 is a tumor suppressor that participates in DNA damage checkpoint signaling cascades. Plk1 phosphorylates, colocalizes with, and interacts with Chk2, suggesting interconnection of DNA damage checkpoints and mitotic regulation. However, the function of their association is unknown. Here, we show that the interaction between Chk2 and Plk1 is cell cycle-regulated, with a peak in mitosis. DNA damage in G2 and M phases but not in S phase induces dissociation of Plk1 and Chk2. In vitro, the Plk1 PBD binds phosphorylated Chk2, and mediates an interaction independent of other eukaryotic proteins. Additionally, a phosphopeptide encompassing phosphoT68 of Chk2 binds Plk1 in a PBD-dependent manner, and stimulates Plk1 activity. These results identify potential mechanisms for interaction and inter-regulation of these two protein kinases.
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