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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
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dc.contributor.author
Muñoz, Inés G.
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Villamor-Payà, Marina
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Jauset, Cristina
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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
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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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
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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
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41467-018-04941-y
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