LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1.
LATS (large tumour suppressor) is a family of conserved tumour suppressors identified in Drosophila and mammals. Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. LATS1 inhibits both the phosphorylation of cofilin by LIMK1 and LIMK1-induced cytokinesis defects. Inactivation of LATS1 by antibody microinjection or RNA-mediated interference in cells, or gene knockout in mice, abrogates cytokinesis and increases the percentage of multinucleate cells. Our findings indicate that LATS1 is a novel cytoskeleton regulator that affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1.
Yang
Xiaolong
X
Howard Hughes Medical Institute, and Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.
Yu
Kuanping
K
Hao
Yawei
Y
Li
Da-ming
DM
Stewart
Rodney
R
Insogna
Karl L
KL
Xu
Tian
T
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological / Q000235:genetics; D005333:Fetus; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D054461:Lim Kinases; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
D051339:Actin Depolymerizing Factors; D000906:Antibodies; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D011108:Polymers; D000205:Actomyosin; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases