Proceedings of the National Academy of Sciences of the United States of America
PubMed Central® ID
Bipolar spindle formation is pivotal for accurate segregation of mitotic chromosomes during cell division. A growing body of evidence suggests that, in addition to centrosome- and chromatin-based microtubule (MT) nucleation, MT-based MT nucleation plays an important role for proper bipolar spindle formation in various eukaryotic organisms. Although a recently discovered Augmin complex appears to play a central role in this event, how Augmin is regulated remains unknown. Here we provide evidence that a mammalian polo-like kinase 1 (Plk1) localizes to mitotic spindles and promotes MT-based MT nucleation by directly regulating Augmin. Mechanistically, we demonstrated that Cdc2-dependent phosphorylation on a γ-tubulin ring complex (γ-TuRC) recruitment protein, Nedd1/GCP-WD, at the previously uncharacterized S460 residue induces the Nedd1-Plk1 interaction. This step appeared to be critical to allow Plk1 to phosphorylate the Hice1 subunit of the Augmin complex to promote the Augmin-MT interaction and MT-based MT nucleation from within the spindle. Loss of either the Nedd1 S460 function or the Plk1-dependent Hice1 phosphorylation impaired both the Augmin-MT interaction and γ-tubulin recruitment to the spindles, thus resulting in improper bipolar spindle formation that ultimately leads to mitotic arrest and apoptotic cell death. Thus, via the formation of the Nedd1-Plk1 complex and subsequent Augmin phosphorylation, Plk1 regulates spindle MT-based MT nucleation to accomplish normal bipolar spindle formation and mitotic progression.
Amino acid sequence, base sequence, binding sites, kinase, cell cycle proteins, DNA primers, microtubules, biological
Johmura, Yoshikazu; Soung, Nak-Kyun; Park, Jung-Eun; Yu, Li-Rong; Zhou, Ming; Bang, Jeong K.; Kim, Bo-Yeon; Veenstra, Timothy D.; Erikson, Raymond L.; and Lee, Kyung S., "Regulation of Microtubule-Based Microtubule Nucleation by Mammalian Polo-Like Kinase 1" (2011). Pharmaceutical Sciences Faculty Publications. 258.