Analysis on a novel checkpoint mechanism by which centrosomal kinases Lats1/2 regulate the chromosomal stability
Project/Area Number |
26430112
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor biology
|
Research Institution | Osaka University |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
NOJIMA Hiroshi 大阪大学, 微生物病研究所, 教授 (30156195)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 染色体不安定性 / キナーゼ / 中心体 / Lats / 細胞質分裂 / Hippo pathway / リン酸化 / チェックポイント / Hippo |
Outline of Final Research Achievements |
Dysregulation of the centrosome cycle promotes the chromosomal instability (CIN), one of the hallmarks of tumor malignancy, thereby inducing centrosome overduplication, multipolar spindle formation, and chromosome missegregation. This suggests that certain centrosomal kinases stringently regulate the mitotic checkpoint. In this study, we found that the centrosomal kinases, Lats1 and Lats2, regulate centrosome duplication, cytokinesis, accurate chromosome segregation, and a nuclear function after DNA damage by phosphorylating various target proteins, such as Cdc25B, CHO1/MKLP1, and INCENP, thereby avoiding the induction of CIN. Therefore, we proposed a model in which the centrosomes function not only as a mitotic spindle pole for microtubule nucleation but also as an important site for crosstalk of signaling pathways in the mitotic checkpoint.
|
Report
(4 results)
Research Products
(31 results)
-
-
[Journal Article] LATS2 Positively Regulates Polycomb Repressive Complex 2.2016
Author(s)
Torigata K, Daisuke O, Mukai S, Hatanaka A, Ohka F, Motooka D, Nakamura S,Ohkawa Y, Yabuta N, Kondo Y, Nojima H.
-
Journal Title
PLoS One
Volume: 11
Issue: 7
Pages: e0158562-e0158562
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
[Journal Article] Comprehensive phenotypic analysis of knockout mice deficient in cyclin G1 and cyclin G2.2016
Author(s)
Ohno S, Ikeda JI, Naito Y, Okuzaki D, Sasakura T, Fukushima K, Nishikawa Y, Ota K, Kato Y, Wang M, Torigata K, Kasama T, Uchihashi T, Miura D, Yabuta N, Morii E, Nojima H.
-
Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 39091-39091
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Cyclin G2: A novel independent prognostic marker in pancreatic cancer.2015
Author(s)
Hasegawa S, Nagano H, Konno M, Eguchi H, Tomokuni A, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Marubashi S, Nishida N, Koseki J, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
-
Journal Title
Oncology Letters
Volume: 10
Pages: 2986-2990
Related Report
Peer Reviewed
-
-
-
[Journal Article] Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP.2015
Author(s)
Chen Q, Zhang N, Xie R, Wang W, Cai J, Choi KS, David KK, Huang B, Yabuta N, Nojima H, Anders RA, Pan D.
-
Journal Title
Genes & Development
Volume: 29
Issue: 12
Pages: 1285-1297
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
[Journal Article] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.2014
Author(s)
Hasegawa S, Eguchi H, Nagano H, Konno M, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Nishida N, Koseki J, Nishimura T, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
-
Journal Title
Br. J. Cancer
Volume: 111
Issue: 8
Pages: 1572-80
DOI
Related Report
Peer Reviewed
-
[Journal Article] Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of Cyclin G-associated kinase and induction of miR-6302014
Author(s)
Sakurai MA, Ozaki Y, Okuzaki D, Naito Y, Sasakura T, Okamoto A, Tabara H, Inoue T, Hagiyama M, Ito A, Yabuta N, and Nojima H.
-
Journal Title
PLoS One
Volume: 9
Issue: 6
Pages: e100124-e100124
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-