Project Details
Projekt
Regulation of mitotic spindle positioning trough SUMO and ubiquitin modifications
Applicant
Dimitris Liakopoulos, Ph.D.
Subject Area
Cell Biology
Term
from 2011 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 197811605
We will investigate the novel role of the ubiquitin-family proteins in regulation of microtubule-actin interactions, which are important for proper mitosis. The protein Kar9, the budding yeast functional homolog of the APC tumor suppressor, mediates interactions of astral microtubules (aMTs) with the septin- and actin-based cytokinetic apparatus. We have shown that Kar9 is regulated by phosphorylation, sumoylation and ubiquitylation. Kar9 sumoylation is required for Kar9 function, but the molecular mechanism of regulation by SUMO is not understood. Ubiquitylation of Kar9 does not control bulk protein turnover, but leads to disassembly of Kar9 complexes and disruption of aMT/actin interactions when aMTs reach the cytokinetic apparatus. We have evidence that SUMO-targeted ubiquitin ligases (STUbLs) mediate Kar9 ubiquitylation at the cytokinetic apparatus. We hypothesize that septin sumoylation and the structure of the Kar9 complex on aMTs are required for STUbL-mediated Kar9 ubiquitylation. The subject of this proposal is to identify the spatial determinants for Kar9 ubiquitylation and study the interplay of phosphorylation, sumoylation and ubiquitylation by reconstituting the Kar9 modification system in vitro.
DFG Programme
Priority Programmes
International Connection
France
