title: Bimodal Interaction of Mammalian Polo-Like Kinase 1 and a Centrosomal Scaffold, Cep192, in the Regulation of Bipolar Spindle Formation.
abstract: Serving as microtubule-organizing centers, centrosomes play a key role in forming bipolar spindles. The mechanism of how centrosomes promote bipolar spindle assembly in various organisms remains largely unknown. A recent study with Xenopus laevis egg extracts suggested that the Plk1 ortholog Plx1 interacts with the phospho-T46 (p-T46) motif of Xenopus Cep192 (xCep192) to form an xCep192-mediated xAurA-Plx1 cascade that is critical for bipolar spindle formation. Here, we demonstrated that in cultured human cells, Cep192 recruits AurA and Plk1 in a cooperative manner, and this event is important for the reciprocal activation of AurA and Plk1. Strikingly, Plk1 interacted with Cep192 through either the p-T44 (analogous to Xenopus p-T46) or the newly identified p-S995 motif via its C-terminal noncatalytic polo-box domain. The interaction between Plk1 and the p-T44 motif was prevalent in the presence of Cep192-bound AurA, whereas the interaction of Plk1 with the p-T995 motif was preferred in the absence of AurA binding. Notably, the loss of p-T44- and p-S995-dependent Cep192-Plk1 interactions induced an additive defect in recruiting Plk1 and γ-tubulin to centrosomes, which ultimately led to a failure in proper bipolar spindle formation and mitotic progression. Thus, we propose that Plk1 promotes centrosome-based bipolar spindle formation by forming two functionally nonredundant complexes with Cep192.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Meng
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lee
authors.forename: Suk-Youl
authors.initials: SY
authors.lastname: Park
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Bang
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D064096:Aurora Kinase A / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; D000097869:Polo-Like Kinase 1; C526596:Cep192 protein, human