On the Regulation and Function of Human Polo-like Kinase 1 (PLK1): Effects of Overexpression on Cell Cycle Progression

Polo-like kinases (Plks) and cancer

“…Antisense oligodeoxynucleotides (ODNs) to Plk1 have also been shown to be effective for inhibition of its expression in tumor cell lines, leading to loss of cell viability and even demonstrating an antitumor activity in A549 xenografts (Elez et al, 2000). Results from transient expression of dominantnegative Plk1 differed from previous antibody microinjection experiments in that most of the mitotic HeLa cells were bipolar and cytokinesis seemed to be disrupted (Mundt et al, 1997). Expression of dominant-negative Plk1 via an adenoviral vector induces programmed cell death in most tumor cells but not in normal human mammary epithelial cells (Conn et al, 2000).…”

Getting in and out of mitosis with Polo-like kinase-1

“…Moreover, involvement of multiple Plk family members in mitotic exit would explain why phosphomutants of MKlp2 result in severe cytokinesis defects, while Plk1 depletion does not interfere with furrow ingression (van Vugt et al, 2004b). In addition, the fact that overexpression of both Plk1 and Plk3 results in multinucleation suggests cytokinesis is regulated by multiple Plk's (Mundt et al, 1997;Conn et al, 2000). Functional redundancy between Plk1 and Plk3 may also play a role in inheritance of cellular organelles during mitosis.…”

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCFβTrCP-dependent Destruction of the APC Inhibitor Emi1

“…Conversely, we detected no Emi1 coprecipitating with Plk1's N-terminal kinase domain (Plk1-NT), indicating that the PBD is required for stable complex formation with Emi1. Despite the absence of the PBD, Plk1-NT reduced Emi1 levels in cell lysates as effectively as did full-length Plk1, presumably because overexpression obviates the need for stable association and because of the higher specific activity of Plk1's kinase domain in the absence of its C terminus (Mundt et al, 1997;Jang et al, 2002). We also found that the N terminus of Emi1, which contains its degron, was sufficient to associate with Plk1, whereas the region of Emi1 containing the F-box and zinc-binding motif was dispensable for this interaction ( Figure 4C).…”