Rho GTPase-independent regulation of mitotic progression by the RhoGEF Net1.
Mol Biol Cell
; 24(17): 2655-67, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23864709
ABSTRACT
Neuroepithelial transforming gene 1 (Net1) is a RhoA-subfamily-specific guanine nucleotide exchange factor that is overexpressed in multiple human cancers and is required for proliferation. Molecular mechanisms underlying its role in cell proliferation are unknown. Here we show that overexpression or knockdown of Net1 causes mitotic defects. Net1 is required for chromosome congression during metaphase and generation of stable kinetochore microtubule attachments. Accordingly, inhibition of Net1 expression results in spindle assembly checkpoint activation. The ability of Net1 to control mitosis is independent of RhoA or RhoB activation, as knockdown of either GTPase does not phenocopy effects of Net1 knockdown on nuclear morphology, and effects of Net1 knockdown are effectively rescued by expression of catalytically inactive Net1. We also observe that Net1 expression is required for centrosomal activation of p21-activated kinase and its downstream kinase Aurora A, which are critical regulators of centrosome maturation and spindle assembly. These results identify Net1 as a novel regulator of mitosis and indicate that altered expression of Net1, as occurs in human cancers, may adversely affect genomic stability.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oncogene Proteins
/
Microtubules
/
Mitosis
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mol Biol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2013
Document type:
Article
Affiliation country:
United States