TY - JOUR
T1 - KIBRA regulates Aurora kinase activity and is required for precise chromosome alignment during mitosis
AU - Zhang, Lin
AU - Iyer, Jyoti
AU - Chowdhury, Aparajita
AU - Ji, Ming
AU - Xiao, Ling
AU - Yang, Shuping
AU - Chen, Yuanhong
AU - Tsai, Ming Ying
AU - Dong, Jixin
PY - 2012/10/5
Y1 - 2012/10/5
N2 - The Hippo pathway controls organ size and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. KIBRA was recently identified as a novel regulator of the Hippo pathway. Several of the components of the Hippo pathway are important regulators of mitosis-related cell cycle events. We recently reported that KIBRA is phosphorylated by the mitotic kinases Aurora-A and -B. However, the role KIBRA plays in mitosis has not been established. Here, we show that KIBRA activates the Aurora kinases and is required for full activation of Aurora kinases during mitosis. KIBRA also promotes the phosphorylation of large tumor suppressor 2 (Lats2) on Ser83 by activating Aurora-A, which controls Lats2 centrosome localization. However, Aurora-A is not required for KIBRA to associate with Lats2. We also found that Lats2 inhibits the Aurora-mediated phosphorylation of KIBRA on Ser539, probably via regulating protein phosphatase 1. Consistent with playing a role in mitosis, siRNA-mediated knockdown of KIBRA causes mitotic abnormalities, including defects of spindle and centrosome formation and chromosome misalignment. We propose that the KIBRA-Aurora-Lats2 protein complexes form a novel axis that regulates precise mitosis.
AB - The Hippo pathway controls organ size and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. KIBRA was recently identified as a novel regulator of the Hippo pathway. Several of the components of the Hippo pathway are important regulators of mitosis-related cell cycle events. We recently reported that KIBRA is phosphorylated by the mitotic kinases Aurora-A and -B. However, the role KIBRA plays in mitosis has not been established. Here, we show that KIBRA activates the Aurora kinases and is required for full activation of Aurora kinases during mitosis. KIBRA also promotes the phosphorylation of large tumor suppressor 2 (Lats2) on Ser83 by activating Aurora-A, which controls Lats2 centrosome localization. However, Aurora-A is not required for KIBRA to associate with Lats2. We also found that Lats2 inhibits the Aurora-mediated phosphorylation of KIBRA on Ser539, probably via regulating protein phosphatase 1. Consistent with playing a role in mitosis, siRNA-mediated knockdown of KIBRA causes mitotic abnormalities, including defects of spindle and centrosome formation and chromosome misalignment. We propose that the KIBRA-Aurora-Lats2 protein complexes form a novel axis that regulates precise mitosis.
UR - http://www.scopus.com/inward/record.url?scp=84867255560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867255560&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.385518
DO - 10.1074/jbc.M112.385518
M3 - Article
C2 - 22904328
AN - SCOPUS:84867255560
SN - 0021-9258
VL - 287
SP - 34069
EP - 34077
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -