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dc.contributor.author
Raab, Monika
dc.contributor.author
Sanhaji, Mourad
dc.contributor.author
Pietsch, Larissa
dc.contributor.author
Béquignon, Isabelle
dc.contributor.author
Herbrand, Amanda K.
dc.contributor.author
Süß, Evelyn
dc.contributor.author
Gande, Santosh L.
dc.contributor.author
Caspar, Birgit
dc.contributor.author
Kudlinzki, Denis
dc.contributor.author
Saxena, Krishna
dc.contributor.author
Sreeramulu, Sridhar
dc.contributor.author
Schwalbe, Harald
dc.contributor.author
Strebhardt, Klaus
dc.contributor.author
Biondi, Ricardo Miguel
dc.date.available
2019-11-13T17:44:18Z
dc.date.issued
2018-08
dc.identifier.citation
Raab, Monika; Sanhaji, Mourad; Pietsch, Larissa; Béquignon, Isabelle; Herbrand, Amanda K.; et al.; Modulation of the Allosteric Communication between the Polo-Box Domain and the Catalytic Domain in Plk1 by Small Compounds; American Chemical Society; ACS Chemical Biology; 13; 8; 8-2018; 1921-1931
dc.identifier.issn
1554-8929
dc.identifier.uri
http://hdl.handle.net/11336/88741
dc.description.abstract
The Polo-like kinases (Plks) are an evolutionary conserved family of Ser/Thr protein kinases that possess, in addition to the classical kinase domain at the N-terminus, a C-terminal polo-box domain (PBD) that binds to phosphorylated proteins and modulates the kinase activity and its localization. Plk1, which regulates the formation of the mitotic spindle, has emerged as a validated drug target for the treatment of cancer, because it is required for numerous types of cancer cells but not for the cell division in noncancer cells. Here, we employed chemical biology methods to investigate the allosteric communication between the PBD and the catalytic domain of Plk1. We identified small compounds that bind to the catalytic domain and inhibit or enhance the interaction of Plk1 with the phosphorylated peptide PoloBoxtide in vitro. In cells, two new allosteric Plk1 inhibitors affected the proliferation of cancer cells in culture and the cell cycle but had distinct phenotypic effects on spindle formation. Both compounds inhibited Plk1 signaling, indicating that they specifically act on Plk1 in cultured cells.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Protein kinase regulation
dc.subject
PLK1
dc.subject
small compounds
dc.subject
allosteric inhibition
dc.subject
protein-protein interaction
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Modulation of the Allosteric Communication between the Polo-Box Domain and the Catalytic Domain in Plk1 by Small Compounds
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-22T17:54:03Z
dc.journal.volume
13
dc.journal.number
8
dc.journal.pagination
1921-1931
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Raab, Monika. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Sanhaji, Mourad. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Pietsch, Larissa. German Cancer Research Center; Alemania. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Béquignon, Isabelle. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Herbrand, Amanda K.. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Süß, Evelyn. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Gande, Santosh L.. German Cancer Research Center; Alemania. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Caspar, Birgit. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Kudlinzki, Denis. Goethe Universitat Frankfurt; Alemania. German Cancer Research Center; Alemania
dc.description.fil
Fil: Saxena, Krishna. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Sreeramulu, Sridhar. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Schwalbe, Harald. Goethe Universitat Frankfurt; Alemania. German Cancer Research Center; Alemania
dc.description.fil
Fil: Strebhardt, Klaus. Goethe Universitat Frankfurt; Alemania. German Cancer Research Center; Alemania
dc.description.fil
Fil: Biondi, Ricardo Miguel. German Cancer Research Center; Alemania. Goethe Universitat Frankfurt; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.journal.title
ACS Chemical Biology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acschembio.7b01078
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acschembio.7b01078
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