| Popis: |
Polo-like kinase 3 (Plk3) is a member of a conserved family of serine/threonine kinases that primarily regulate cell cycle progression and mitotic events. In response to ionizing radiation, Plk3 facilitates the activation of G1/S checkpoint arrest. Further, published data from our lab suggested that Plk3 may be capable of activating G1/S checkpoint arrest independent of p53 signaling. The tumor suppressor protein p53 is the central hub of DNA damage response signaling and the most frequently deleted or mutated gene in cancers. A Plk3-dependent, p53-independent mechanism for G1/S checkpoint arrest could partially compensate for the loss of p53 function. Therefore, in our first project, we investigated the hypothesis that the combined loss of p53 and Plk3 would be synthetic lethal with cell death resulting from the abolishment of the G1/S checkpoint and the accumulation of unrepaired DNA damage. However, our experimental results did not support our hypothesis and we decided to shift to a new project. The Plk literature also suggests that Plk3 may have additional roles associated with normal cell function. Here, mouse embryonic fibroblasts generated from Plk3 knockout or wildtype mice were compared, to identify alternative functions for Plk3 in addition to its canonical role. Specifically, Plk3 has been reported to associate with key proteins involved in cytoskeletal organization; co-localizing with f-actin and directly phosphorylating ß-tubulin. These and other data suggested a role for Plk3 in regulation of the cytoskeleton and cell morphology. To this end, given the importance of dynamic cytoskeletal rearrangement to cell motility, we analyzed whether Plk3 is involved in cell migration, attachment and/or invasion using Plk3 knockout mouse embryonic fibroblasts. |
