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@ARTICLE{HnleKreidler:182682,
author = {S. Hänle-Kreidler$^*$ and K. Richter$^*$ and I.
Hoffmann$^*$},
title = {{T}he {SCF}-{FBXW}7 {E}3 ubiquitin ligase triggers
degradation of {H}istone 3 {L}ysine 4 methyltransferase
complex component {WDR}5 to prevent mitotic slippage.},
journal = {The journal of biological chemistry},
volume = {298},
number = {12},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {DKFZ-2022-02850},
pages = {102703},
year = {2022},
note = {ISSN 0021-9258 / #EA:F045#LA:F045#},
abstract = {During prolonged mitotic arrest induced by anti-microtubule
drugs, cell fate decision is determined by two alternative
pathways, one leading to cell death, the other inducing
premature escape from mitosis by mitotic slippage. FBWX7, a
member of the F-box family of proteins and
substrate-targeting subunit of the SCF (SKP1-CUL1-F-Box) E3
ubiquitin ligase complex promotes mitotic cell death and
prevents mitotic slippage, but molecular details underlying
these roles for FBWX7 are unclear. In this study, we report
that WDR5, a component of the mixed lineage leukemia (MLL)
complex of Histone 3 Lysine 4 (H3K4) methyltransferases, is
a substrate of FBXW7. We determined by
co-immunoprecipitation experiments and in vitro binding
assays that WDR5 interacts with FBXW7 in vivo and in vitro.
SCF-FBXW7 mediates ubiquitination of WDR5 and targets it for
proteasomal degradation. Furthermore, we find that WDR5
depletion counteracts FBXW7 loss-of-function by reducing
mitotic slippage and polyploidization. In conclusion, our
data elucidate a new mechanism in mitotic cell fate
regulation which might contribute to prevent chemotherapy
resistance in patients after anti-microtubule drug
treatment.},
keywords = {FBXW7 (Other) / WDR5 (Other) / chemoresistance (Other) /
mitotic slippage (Other) / ubiquitylation (ubiquitination)
(Other)},
cin = {F045},
ddc = {540},
cid = {I:(DE-He78)F045-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36395886},
doi = {10.1016/j.jbc.2022.102703},
url = {https://inrepo02.dkfz.de/record/182682},
}