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Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1
during cytokinesis
#MMPMID25786116
Okamoto A
; Yabuta N
; Mukai S
; Torigata K
; Nojima H
Cell Cycle
2015[]; 14
(10
): 1568-82
PMID25786116
show ga
Large tumor suppressor 1 and 2 (Lats1/2) regulate centrosomal integrity,
chromosome segregation and cytokinesis. As components of the centralspindlin
complex, the kinesin-like protein CHO1 and its splicing variant MKLP1 colocalize
with chromosome passenger proteins and GTPases and regulate the formation of the
contractile ring and cytokinesis; however, the regulatory mechanisms of
CHO1/MKLP1 remain elusive. Here, we show that Lats1/2 phosphorylate Ser716 in the
F-actin-interacting region of CHO1, which is absent in MKLP1. Phosphorylated CHO1
localized to the centrosomes and midbody, and the actin polymerization factor
LIM-kinase 1 (LIMK1) was identified as its binding partner. Overexpression of
constitutively phosphorylated and non-phosphorylated CHO1 altered the mitotic
localization and activation of LIMK1 at the centrosomes in HeLa cells, leading to
the inhibition of cytokinesis through excessive phosphorylation of Cofilin and
mislocalization of Ect2. These results suggest that Lats1/2 stringently control
cytokinesis by regulating CHO1 phosphorylation and the mitotic activation of
LIMK1 on centrosomes.
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