Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1 interaction is critical for proper chromosome segregation.
The polo-box domain (PBD) of mammalian polo-like kinase 1 (Plk1) is essential in targeting its catalytic activity to specific subcellular structures critical for mitosis. The mechanism underlying Plk1 recruitment to the kinetochores and the role of Plk1 at this site remain elusive. Here, we demonstrate that a PBD-binding protein, PBIP1, is crucial for recruiting Plk1 to the interphase and mitotic kinetochores. Unprecedentedly, Plk1 phosphorylated PBIP1 at T78, creating a self-tethering site that specifically interacted with the PBD of Plk1, but not Plk2 or Plk3. Later in mitosis, Plk1 also induced PBIP1 degradation in a T78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions. Absence of the p-T78-dependent Plk1 localization induced a chromosome congression defect and compromised the spindle checkpoint, ultimately leading to aneuploidy. Thus, Plk1 self-regulates the Plk1-PBIP1 interaction to timely localize to the kinetochores and promote proper chromosome segregation.
Kang
Young H
YH
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Park
Jung-Eun
JE
Yu
Li-Rong
LR
Soung
Nak-Kyun
NK
Yun
Sang-Moon
SM
Bang
Jeong K
JK
Seong
Yeon-Sun
YS
Yu
Hongtao
H
Garfield
Susan
S
Veenstra
Timothy D
TD
Lee
Kyung S
KS
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics*; D000939:Epitopes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D049468:Prometaphase / Q000502:physiology; D011418:Prophase / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000939:Epitopes; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012694:Serine; D013912:Threonine; D000097869:Polo-Like Kinase 1