TY  - JOUR
A1  - Melo-Hanchuk, Talita D.
A1  - Ferreira Slepicka, Priscila
A1  - Vaz Meirelles, Gabriela
A1  - Basei, Fernanda Luisa
A1  - Ventura Lovato, Diogo
A1  - Campos Granato, Daniela
A1  - Alves Pauletti, Bianca
A1  - Ramos Domingues, Romenia
A1  - Paes Leme, Adriana Franco
A1  - Pelegrini, Alessandra Luiza
A1  - Lenz, Guido
A1  - Knapp, Stefan
A1  - Elkins, Jonathan M.
A1  - Kobarg, Jörg
T1  - NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
T2  - Scientific reports
N2  - 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.
KW  - Enzymes
KW  - Structural biology
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45665
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456652
SN  - 2045-2322
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
VL  - 7
IS  - 1, Art. 5445
SP  - 1
EP  - 13
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -