NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin

Abstract NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Talita D. Melo-Hanchuk, Priscila Ferreira Slepicka, Gabriela Vaz Meirelles, Fernanda Luisa Basei, Diogo Ventura Lovato, Daniela Campos Granato, Bianca Alves Pauletti, Romenia Ramos Domingues, Adriana Franco Paes Leme, Alessandra Luiza Pelegrini, Guido Lenz, Stefan Knapp, Jonathan M. Elkins, Jörg Kobarg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80bf2f9526eb4999bda5f11ee8002f15
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:80bf2f9526eb4999bda5f11ee8002f15
record_format	dspace
spelling	oai:doaj.org-article:80bf2f9526eb4999bda5f11ee8002f152021-12-02T12:32:26ZNEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin10.1038/s41598-017-05325-w2045-2322https://doaj.org/article/80bf2f9526eb4999bda5f11ee8002f152017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05325-whttps://doaj.org/toc/2045-2322Abstract NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.Talita D. Melo-HanchukPriscila Ferreira SlepickaGabriela Vaz MeirellesFernanda Luisa BaseiDiogo Ventura LovatoDaniela Campos GranatoBianca Alves PaulettiRomenia Ramos DominguesAdriana Franco Paes LemeAlessandra Luiza PelegriniGuido LenzStefan KnappJonathan M. ElkinsJörg KobargNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Talita D. Melo-Hanchuk Priscila Ferreira Slepicka Gabriela Vaz Meirelles Fernanda Luisa Basei Diogo Ventura Lovato Daniela Campos Granato Bianca Alves Pauletti Romenia Ramos Domingues Adriana Franco Paes Leme Alessandra Luiza Pelegrini Guido Lenz Stefan Knapp Jonathan M. Elkins Jörg Kobarg NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
description	Abstract NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.
format	article
author	Talita D. Melo-Hanchuk Priscila Ferreira Slepicka Gabriela Vaz Meirelles Fernanda Luisa Basei Diogo Ventura Lovato Daniela Campos Granato Bianca Alves Pauletti Romenia Ramos Domingues Adriana Franco Paes Leme Alessandra Luiza Pelegrini Guido Lenz Stefan Knapp Jonathan M. Elkins Jörg Kobarg
author_facet	Talita D. Melo-Hanchuk Priscila Ferreira Slepicka Gabriela Vaz Meirelles Fernanda Luisa Basei Diogo Ventura Lovato Daniela Campos Granato Bianca Alves Pauletti Romenia Ramos Domingues Adriana Franco Paes Leme Alessandra Luiza Pelegrini Guido Lenz Stefan Knapp Jonathan M. Elkins Jörg Kobarg
author_sort	Talita D. Melo-Hanchuk
title	NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
title_short	NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
title_full	NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
title_fullStr	NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
title_full_unstemmed	NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
title_sort	nek1 kinase domain structure and its dynamic protein interactome after exposure to cisplatin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/80bf2f9526eb4999bda5f11ee8002f15
work_keys_str_mv	AT talitadmelohanchuk nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT priscilaferreiraslepicka nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT gabrielavazmeirelles nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT fernandaluisabasei nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT diogoventuralovato nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT danielacamposgranato nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT biancaalvespauletti nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT romeniaramosdomingues nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT adrianafrancopaesleme nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT alessandraluizapelegrini nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT guidolenz nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT stefanknapp nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT jonathanmelkins nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin AT jorgkobarg nek1kinasedomainstructureanditsdynamicproteininteractomeafterexposuretocisplatin
_version_	1718394103826219008

NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin

Ejemplares similares