Pharmaceutical Sciences Faculty Publications
Document Type
Article
Publication Date
7-12-2011
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
ISSN
1091-6490
Volume
108
Issue
28
First Page
11446
Last Page
11451
DOI
10.1073/pnas.1106223108
PubMed ID
21690413
PubMed Central® ID
PMC3136274
Abstract
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.
Keywords
Amino acid sequence, base sequence, binding sites, kinase, cell cycle proteins, DNA primers, microtubules, biological
Recommended Citation
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.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/258
