Regulation of a LATS-homolog by Ras GTPases is important for the control of cell divisionReport as inadecuate




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BMC Cell Biology

, 15:25

Cell division and cell cycle control

Abstract

BackgroundNuclear Dbf-related-large tumor suppressor NDR-LATS kinases have been shown recently to control pathways that regulate mitotic exit, cytokinesis, cell growth, morphological changes and apoptosis. LATS kinases are core components of the Hippo signaling cascade and important tumor suppressors controlling cell proliferation and organ size in flies and mammals, and homologs are also present in yeast and Dictyostelium discoideum. Ras proto-oncogens regulate many biological functions, including differentiation, proliferation and apoptosis. Dysfunctions of LATS kinases or Ras GTPases have been implicated in the development of a variety of cancers in humans.

ResultsIn this study we used the model organism Dictyostelium discoideum to analyze the functions of NdrC, a homolog of the mammalian LATS2 protein, and present a novel regulatory mechanism for this kinase. Deletion of the ndrC gene caused impaired cell division and loss of centrosome integrity. A yeast two-hybrid analysis, using activated Ras proteins as bait, revealed NdrC as an interactor and identified its Ras-binding domain. Further in vitro pull-down assays showed that NdrC binds RasG and RasB, and to a lesser extent RasC and Rap1. In cells lacking NdrC, the levels of activated RasB and RasG are up-regulated, suggesting a functional connection between RasB, RasG, and NdrC.

ConclusionsDictyostelium discoideum NdrC is a LATS2-homologous kinase that is important for the regulation of cell division. NdrC contains a Ras-binding domain and interacts preferentially with RasB and RasG. Changed levels of both, RasB or RasG, have been shown previously to interfere with cell division. Since a defect in cell division is exhibited by NdrC-null cells, RasG-null cells, and cells overexpressing activated RasB, we propose a model for the regulation of cytokinesis by NdrC that involves the antagonistic control by RasB and RasG.

KeywordsCell division Dictyostelium discoideum Ras GTPase LATS kinase AbbreviationsaaAmino acids

GSTGlutathione-S-transferase.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-15-25 contains supplementary material, which is available to authorized users.

Annette Müller-Taubenberger, Peter M Kastner contributed equally to this work.

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Author: Annette Müller-Taubenberger - Peter M Kastner - Michael Schleicher - Parvin Bolourani - Gerald Weeks

Source: https://link.springer.com/



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