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@ARTICLE{Gregorczyk:276083,
author = {M. Gregorczyk and G. Pastore and I. Muñoz and T. Carroll
and J. Streubel$^*$ and M. Munro and P. Lis and S. Lange and
F. Lamoliatte and T. Macartney and R. Toth and F. Brown and
J. Hastie and G. Pereira$^*$ and D. Durocher and J. Rouse},
title = {{F}unctional characterization of {C}21{ORF}2 association
with the {NEK}1 kinase mutated in human in diseases.},
journal = {Life science alliance},
volume = {6},
number = {7},
issn = {2575-1077},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2023-00989},
pages = {e202201740 -},
year = {2023},
note = {DKFZ-ZMBH Alliance},
abstract = {The NEK1 kinase controls ciliogenesis, mitosis, and DNA
repair, and NEK1 mutations cause human diseases including
axial spondylometaphyseal dysplasia and amyotrophic lateral
sclerosis. C21ORF2 mutations cause a similar pattern of
human diseases, suggesting close functional links with NEK1
Here, we report that endogenous NEK1 and C21ORF2 form a
tight complex in human cells. A C21ORF2 interaction domain
'CID' at the C-terminus of NEK1 is necessary for its
association with C21ORF2 in cells, and pathogenic mutations
in this region disrupt the complex. AlphaFold modelling
predicts an extended binding interface between a
leucine-rich repeat domain in C21ORF2 and the NEK1-CID, and
our model may explain why pathogenic mutations perturb the
complex. We show that NEK1 mutations that inhibit kinase
activity or weaken its association with C21ORF2 severely
compromise ciliogenesis, and that C21ORF2, like NEK1 is
required for homologous recombination. These data enhance
our understanding of how the NEK1 kinase is regulated, and
they shed light on NEK1-C21ORF2-associated diseases.},
keywords = {Humans / NIMA-Related Kinase 1: genetics / Mutation:
genetics / DNA Repair / Osteochondrodysplasias: genetics /
Phosphorylation / NIMA-Related Kinase 1 (NLM Chemicals) /
NEK1 protein, human (NLM Chemicals)},
cin = {A180},
ddc = {570},
cid = {I:(DE-He78)A180-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37188479},
pmc = {pmc:PMC10185812},
doi = {10.26508/lsa.202201740},
url = {https://inrepo02.dkfz.de/record/276083},
}