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dc.creatorDadke, Disha
dc.creatorJarnik, Michael
dc.creatorPugacheva, Elena N.
dc.creatorSingh, Mahendra K.
dc.creatorGolemis, Erica
dc.identifier.citationDadke D, Jarnik M, Pugacheva EN, Singh MK, Golemis EA. Deregulation of HEF1 Impairs M-Phase Progression by Disrupting the RhoA Activation Cycle. Mol Bio Cell. 2006 Jan 4;17(3):1204-1217. doi:10.1091/mbc.e05-03-0237.
dc.description.abstractThe focal adhesion-associated signaling protein HEF1 undergoes a striking relocalization to the spindle at mitosis, but a function for HEF1 in mitotic signaling has not been demonstrated. We here report that overexpression of HEF1 leads to failure of cells to progress through cytokinesis, whereas depletion of HEF1 by small interfering RNA (siRNA) leads to defects earlier in M phase before cleavage furrow formation. These defects can be explained mechanistically by our determination that HEF1 regulates the activation cycle of RhoA. Inactivation of RhoA has long been known to be required for cytokinesis, whereas it has recently been determined that activation of RhoA at the entry to M phase is required for cellular rounding. We find that increased HEF1 sustains RhoA activation, whereas depleted HEF1 by siRNA reduces RhoA activation. Furthermore, we demonstrate that chemical inhibition of RhoA is sufficient to reverse HEF1-dependent cellular arrest at cytokinesis. Finally, we demonstrate that HEF1 associates with the RhoA-GTP exchange factor ECT2, an orthologue of the Drosophila cytokinetic regulator Pebble, providing a direct means for HEF1 control of RhoA. We conclude that HEF1 is a novel component of the cell division control machinery and that HEF1 activity impacts division as well as cell attachment signaling events.
dc.format.extent14 pages
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartMolecular Biology of the Cell, Vol. 17, No. 3
dc.relation.isreferencedbyAmerican Society for Cell Biology
dc.rightsAttribution-NonCommercial-ShareAlike CC BY-NC-SA
dc.titleDeregulation of HEF1 Impairs M-Phase Progression by Disrupting the RhoA Activation Cycle
dc.type.genreJournal article
dc.contributor.groupFox Chase Cancer Center (Temple University)
dc.description.departmentCancer and Cellular Biology
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.description.schoolcollegeLewis Katz School of Medicine
dc.temple.creatorDadke, Disha
dc.temple.creatorJarnik, Michael
dc.temple.creatorPugacheva, Elena N.
dc.temple.creatorSingh, Mahendra K.
dc.temple.creatorGolemis, Erica A.

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