Article ; Online: Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1 during cytokinesis.
2015 Volume 14, Issue 10, Page(s) 1568–1582
Abstract: ... by regulating CHO1 phosphorylation and the mitotic activation of LIMK1 on centrosomes. ... Large tumor suppressor 1 and 2 (Lats1/2) regulate centrosomal integrity, chromosome segregation and ... we show that Lats1/2 phosphorylate Ser716 in the F-actin-interacting region of CHO1, which is absent ...
| Abstract | 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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| MeSH term(s) | Centrosome/metabolism ; Cofilin 1/metabolism ; Cytokinesis/physiology ; HEK293 Cells ; HeLa Cells ; Humans ; Lim Kinases/metabolism ; Microscopy, Fluorescence ; Microtubule-Associated Proteins/antagonists & inhibitors ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Mitosis ; Phosphorylation ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Signal Transduction ; Tumor Suppressor Proteins/antagonists & inhibitors ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism | |||||
| Chemical Substances | Cofilin 1 ; ECT2 protein, human ; KIF23 protein, human ; Microtubule-Associated Proteins ; Proto-Oncogene Proteins ; RNA, Small Interfering ; Tumor Suppressor Proteins ; LATS1 protein, human (EC 2.7.1.-) ; LATS2 protein, human (EC 2.7.1.11) ; LIMK1 protein, human (EC 2.7.11.1) ; Lim Kinases (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) | |||||
| Language | English | |||||
| Publishing date | 2015-03-18 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2146183-1 | |||||
| ISSN | 1551-4005 ; 1538-4101 ; 1554-8627 | |||||
| ISSN (online) | 1551-4005 | |||||
| ISSN | 1538-4101 ; 1554-8627 | |||||
| DOI | 10.1080/15384101.2015.1026489 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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