title: Mammalian polo-like kinase 1-dependent regulation of the PBIP1-CENP-Q complex at kinetochores.
abstract: Mammalian polo-like kinase 1 (Plk1) plays a pivotal role during M-phase progression. Plk1 localizes to specific subcellular structures through the targeting activity of the C-terminal polo-box domain (PBD). Disruption of the PBD function results in improper bipolar spindle formation, chromosome missegregation, and cytokinesis defect that ultimately lead to the generation of aneuploidy. It has been shown that Plk1 recruits itself to centromeres by phosphorylating and binding to a centromere scaffold, PBIP1 (also called MLF1IP and CENP-U[50]) through its PBD. However, how PBIP1 itself is targeted to centromeres and what roles it plays in the regulation of Plk1-dependent mitotic events remain unknown. Here, we demonstrated that PBIP1 directly interacts with CENP-Q, and this interaction was mutually required not only for their stability but also for their centromere localization. Plk1 did not appear to interact with CENP-Q directly. However, Plk1 formed a ternary complex with PBIP1 and CENP-Q through a self-generated p-T78 motif on PBIP1. This complex formation was central for Plk1-dependent phosphorylation of PBIP1-bound CENP-Q and delocalization of the PBIP1-CENP-Q complex from mitotic centromeres. This study reveals a unique mechanism of how PBIP1 mediates Plk1-dependent phosphorylation event onto a third protein, and provides new insights into the mechanism of how Plk1 and its recruitment scaffold, PBIP1-CENP-Q complex, are localized to and delocalized from centromeres.
authors: Laboratory of Metabolism, Center for Cancer Research, NCI National Institutes of Health, Bethesda, Maryland 20892-4258, USA.
authors: Young H
authors: YH
authors: Kang
authors: Chi Hoon
authors: CH
authors: Park
authors: Tae-Sung
authors: TS
authors: Kim
authors: Nak-Kyun
authors: NK
authors: Soung
authors: Jeong K
authors: JK
authors: Bang
authors: Bo Y
authors: BY
authors: Kim
authors: Jung-Eun
authors: JE
authors: Park
authors: Kyung S
authors: KS
authors: Lee
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002417:Cattle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C559900:CENPQ protein, human; C485917:CENPU protein, human; C585527:MLF1-IP protein, mouse