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|Title:||Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction|
|Authors:||Mardin, Balca R.|
Baxter, Joanne E.
Scholz, Sebastian R.
Fry, Andrew M.
|Publisher:||Nature Publishing Group|
|Citation:||Nature Cell Biology, 2010, 12 (12), pp. 1166-1176|
|Abstract:||During interphase, centrosomes are held together by a proteinaceous linker that connects the proximal ends of the mother and daughter centriole. This linker is disassembled at the onset of mitosis in a process known as centrosome disjunction, thereby facilitating centrosome separation and bipolar spindle formation. The NIMA (never in mitosis A)-related kinase Nek2A is implicated in disconnecting the centrosomes through disjoining the linker proteins C-Nap1 and rootletin. However, the mechanisms controlling centrosome disjunction remain poorly understood. Here, we report that two Hippo pathway components, the mammalian sterile 20-like kinase 2 (Mst2) and the scaffold protein Salvador (hSav1), directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin. Furthermore, we demonstrate that the hSav1–Mst2–Nek2A centrosome disjunction pathway becomes essential for bipolar spindle formation on partial inhibition of the kinesin-5 Eg5. We propose that hSav1–Mst2–Nek2A and Eg5 have distinct, but complementary functions, in centrosome disjunction.|
|Rights:||Copyright © 2010 Macmillan Publishers Limited. All rights reserved. Deposited with reference to the publisher’s open access archiving policy.|
|Appears in Collections:||Published Articles, Dept. of Biochemistry|
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