Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-19471-2
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dc.titleGroup-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its oligomerization state and Rac1 ubiquitination
dc.contributor.authorAcosta, M.I
dc.contributor.authorUrbach, S
dc.contributor.authorDoye, A
dc.contributor.authorNg, Y.-W
dc.contributor.authorBoudeau, J
dc.contributor.authorMettouchi, A
dc.contributor.authorDebant, A
dc.contributor.authorManser, E
dc.contributor.authorVisvikis, O
dc.contributor.authorLemichez, E
dc.date.accessioned2020-10-20T10:01:12Z
dc.date.available2020-10-20T10:01:12Z
dc.date.issued2018
dc.identifier.citationAcosta, M.I, Urbach, S, Doye, A, Ng, Y.-W, Boudeau, J, Mettouchi, A, Debant, A, Manser, E, Visvikis, O, Lemichez, E (2018). Group-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its oligomerization state and Rac1 ubiquitination. Scientific Reports 8 (1) : 1410. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-19471-2
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178469
dc.description.abstractThe regulation of Rac1 by HACE1-mediated ubiquitination and proteasomal degradation is emerging as an essential element in the maintenance of cell homeostasis. However, how the E3 ubiquitin ligase activity of HACE1 is regulated remains undetermined. Using a proteomic approach, we identified serine 385 as a target of group-I PAK kinases downstream Rac1 activation by CNF1 toxin from pathogenic E. coli. Moreover, cell treatment with VEGF also promotes Ser-385 phosphorylation of HACE1. We have established in vitro that HACE1 is a direct target of PAK1 kinase activity. Mechanistically, we found that the phospho-mimetic mutant HACE1(S385E), as opposed to HACE1(S385A), displays a lower capacity to ubiquitinate Rac1 in cells. Concomitantly, phosphorylation of Ser-385 plays a pivotal role in controlling the oligomerization state of HACE1. Finally, Ser-385 phosphorylated form of HACE1 localizes in the cytosol away from its target Rac1. Together, our data point to a feedback inhibition of HACE1 ubiquitination activity on Rac1 by group-I PAK kinases. © 2018 The Author(s).
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectbacterial toxin
dc.subjectcytotoxic necrotizing factor 1
dc.subjectEscherichia coli protein
dc.subjectHACE1 protein, human
dc.subjectp21 activated kinase
dc.subjectRac1 protein
dc.subjectRAC1 protein, human
dc.subjectserine
dc.subjectubiquitin protein ligase
dc.subjectvasculotropin A
dc.subjectcell line
dc.subjectchemistry
dc.subjecthuman
dc.subjectmetabolism
dc.subjectphosphorylation
dc.subjectprotein multimerization
dc.subjectproteomics
dc.subjectubiquitination
dc.subjectumbilical vein endothelial cell
dc.subjectBacterial Toxins
dc.subjectCell Line
dc.subjectEscherichia coli Proteins
dc.subjectHuman Umbilical Vein Endothelial Cells
dc.subjectHumans
dc.subjectp21-Activated Kinases
dc.subjectPhosphorylation
dc.subjectProtein Multimerization
dc.subjectProteomics
dc.subjectrac1 GTP-Binding Protein
dc.subjectSerine
dc.subjectUbiquitin-Protein Ligases
dc.subjectUbiquitination
dc.subjectVascular Endothelial Growth Factor A
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1038/s41598-018-19471-2
dc.description.sourcetitleScientific Reports
dc.description.volume8
dc.description.issue1
dc.description.page1410
dc.published.statepublished
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