| First Author | Yeh TY | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 7 | Pages | 1023-35 |
| PubMed ID | 23455152 | Mgi Jnum | J:195306 |
| Mgi Id | MGI:5477876 | Doi | 10.1038/emboj.2013.30 |
| Citation | Yeh TY, et al. (2013) Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit. EMBO J 32(7):1023-35 |
| abstractText | Dynactin is a protein complex required for the in vivo function of cytoplasmic dynein, a microtubule (MT)-based motor. Dynactin binds both dynein and MTs via its p150(Glued) subunit, but little is known about the 'pointed-end complex' that includes the protein subunits Arp11, p62 and the p27/p25 heterodimer. Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin-dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo-like kinase 1 (Plk1) at kinetochores. Removal of p27/p25 from dynactin results in reduced levels of Plk1 and its phosphorylated substrates at kinetochores in prometaphase, which correlates with aberrant kinetochore-MT interactions, improper chromosome alignment and abbreviated mitosis. To investigate the structural implications of p27 phosphorylation, we determined the structure of human p27. This revealed an unusual left-handed beta-helix domain, with the phosphorylation site located within a disordered, C-terminal segment. We conclude that dynactin plays a previously undescribed regulatory role in the spindle assembly checkpoint by recruiting Plk1 to kinetochores and facilitating phosphorylation of important downstream targets. |
