Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression

Department of Biochemistry, Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
Oncogene (Impact Factor: 8.46). 09/2008; 27(52):6635-45. DOI: 10.1038/onc.2008.262
Source: PubMed


Polo-like kinase 1 (Plk1), the best characterized member of the mammalian polo-like kinase family, is well regulated throughout the cell cycle at the protein expression level. Moreover, it is known that Plk1 kinase activity is also regulated at the post-translational level through phosphorylation. However, the upstream kinases of Plk1 have not been identified. Although the involvement of the p38 MAP kinase pathway in cellular responses to stress has been well documented, the role of this pathway in normal cell cycle progression is unclear. Here, we show that phosphorylated p38 and MAP kinase-activated protein kinase 2 (MK2) are colocalized with Plk1 to the spindle poles during prophase and metaphase. Specific depletion of various members of the p38 MAP kinase pathway by the use of RNA interference revealed that the pathway is required for mitotic progression under normal growth conditions. Furthermore, MK2 directly phosphorylates Ser326 of Plk1. Ectopic expression of Plk1-S326A completely blocked cells at mitosis, likely due to the defect of bipolar spindle formation and subsequent activation of the spindle checkpoint. Only Plk1-S326E, but not the Plk1-S326A, efficiently rescued the p38 or MK2-depletion-induced mitotic defects, further solidifying the requirement of S326 phosphorylation during mitotic progression.

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    • "The expression of a mutant Plk1 or depletion of Plk1 caused spindle pole defects, accumulation of cells at the M phase, and massive cell death (Guan et al., 2005; Reagan-Shaw and Ahmad, 2005; Bu et al., 2008). Tang et al. (2008) described how MK2 colocalizes with activated p38 MAPK and Plk1 at spindle poles where it phosphorylates Plk1 at Ser326 to promote normal mitotic progression (Fig. 2D). Importantly, the same study reported that MK2 acts as a Plk1 kinase and that MK2 knockdown resulted in mitotic arrest. "
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