The Plk1 Polo box domain mediates a cell cycle and DNA damage regulated interaction with Chk2.
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.
Tsvetkov
Lyuben M
LM
Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA. ltsvetkov@rigel.com
Tsekova
Rumiana T
RT
Xu
Xingzhi
X
Stern
David F
DF
D000818:Animals; D020134:Catalytic Domain; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D002469:Cell Separation; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008938:Mitosis; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D005982:Glutathione Transferase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C578634:CHEK2 protein, human