title: Polo-like kinase 1 and Chk2 interact and co-localize to centrosomes and the midbody.
abstract: Chk2 is a protein kinase intermediary in DNA damage checkpoint pathways. DNA damage induces phosphorylation of Chk2 at multiple sites concomitant with activation. Chk2 phosphorylated at Thr-68 is found in nuclear foci at sites of DNA damage (1). We report here that Chk2 phosphorylated at Thr-68 and Thr-26 or Ser-28 is localized to centrosomes and midbodies in the absence of DNA damage. In a search for interactions between Chk2 and proteins with similar subcellular localization patterns, we found that Chk2 coimmunoprecipitates with Polo-like kinase 1, a regulator of chromosome segregation, mitotic entry, and mitotic exit. Plk1 overexpression enhances phosphorylation of Chk2 at Thr-68. Plk1 phosphorylates recombinant Chk2 in vitro. Indirect immunofluorescence (IF) microscopy revealed the co-localization of Chk2 and Plk1 to centrosomes in early mitosis and to the midbody in late mitosis. These findings suggest lateral communication between the DNA damage and mitotic checkpoints.
authors.affiliation: Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06511, USA.
authors.forename: Lyuben
authors.initials: L
authors.lastname: Tsvetkov
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: David F
authors.initials: DF
authors.lastname: Stern
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D006801:Humans; D008856:Microscopy, Fluorescence; D010957:Plasmids; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D000097869:Polo-Like Kinase 1; C578634:CHEK2 protein, human