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dc.contributor.author
Mortuza, Gulnahar B.  
dc.contributor.author
Hermida, Dario  
dc.contributor.author
Pedersen, Anna-Kathrine  
dc.contributor.author
Segura-Bayona, Sandra  
dc.contributor.author
López-Méndez, Blanca  
dc.contributor.author
Redondo, Pilar  
dc.contributor.author
Rüther, Patrick  
dc.contributor.author
Pozdnyakova, Irina  
dc.contributor.author
Garrote López, Ana Marcela  
dc.contributor.author
Muñoz, Inés G.  
dc.contributor.author
Villamor-Payà, Marina  
dc.contributor.author
Jauset, Cristina  
dc.contributor.author
Olsen, Jesper V.  
dc.contributor.author
Stracker, Travis H.  
dc.contributor.author
Montoya, Guillermo  
dc.date.available
2023-09-06T14:50:24Z  
dc.date.issued
2018-12  
dc.identifier.citation
Mortuza, Gulnahar B.; Hermida, Dario; Pedersen, Anna-Kathrine; Segura-Bayona, Sandra; López-Méndez, Blanca; et al.; Molecular basis of Tousled-Like Kinase 2 activation; Nature Publishing Group; Nature Communications; 9; 1; 12-2018  
dc.identifier.issn
2041-1723  
dc.identifier.uri
http://hdl.handle.net/11336/210686  
dc.description.abstract
Tousled-like kinases (TLKs) are required for genome stability and normal development in numerous organisms and have been implicated in breast cancer and intellectual disability. In humans, the similar TLK1 and TLK2 interact with each other and TLK activity enhances ASF1 histone binding and is inhibited by the DNA damage response, although the molecular mechanisms of TLK regulation remain unclear. Here we describe the crystal structure of the TLK2 kinase domain. We show that the coiled-coil domains mediate dimerization and are essential for activation through ordered autophosphorylation that promotes higher order oligomers that locally increase TLK2 activity. We show that TLK2 mutations involved in intellectual disability impair kinase activity, and the docking of several small-molecule inhibitors of TLK activity suggest that the crystal structure will be useful for guiding the rationale design of new inhibition strategies. Together our results provide insights into the structure and molecular regulation of the TLKs.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
TLK  
dc.subject
chromatine structure  
dc.subject
kinase activity  
dc.subject.classification
Bioquímica y Biología Molecular  
dc.subject.classification
Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Molecular basis of Tousled-Like Kinase 2 activation  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2023-09-06T11:21:28Z  
dc.journal.volume
9  
dc.journal.number
1  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Mortuza, Gulnahar B.. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Hermida, Dario. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Pedersen, Anna-Kathrine. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Segura-Bayona, Sandra. Irb Barcelona - Institute For Research In Biomedicine; España  
dc.description.fil
Fil: López-Méndez, Blanca. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Redondo, Pilar. Centro Nacional de Investigaciones Oncológicas; España  
dc.description.fil
Fil: Rüther, Patrick. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Pozdnyakova, Irina. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Garrote López, Ana Marcela. Centro Nacional de Investigaciones Oncológicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones En Biodiversidad y Biotecnología. Grupo de Investigación en Química Analítica y Modelado Molecular; Argentina  
dc.description.fil
Fil: Muñoz, Inés G.. Centro Nacional de Investigaciones Oncológicas; España  
dc.description.fil
Fil: Villamor-Payà, Marina. Irb Barcelona - Institute For Research In Biomedicine; España  
dc.description.fil
Fil: Jauset, Cristina. Irb Barcelona - Institute For Research In Biomedicine; España  
dc.description.fil
Fil: Olsen, Jesper V.. Faculty Of Health And Medical Sciences; Dinamarca  
dc.description.fil
Fil: Stracker, Travis H.. Irb Barcelona - Institute For Research In Biomedicine; España  
dc.description.fil
Fil: Montoya, Guillermo. Faculty Of Health And Medical Sciences; Dinamarca  
dc.journal.title
Nature Communications  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41467-018-04941-y