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@ARTICLE{Richter:144403,
author = {K. Richter$^*$ and Y. T. Kschonsak$^*$ and B. Vodicska$^*$
and I. Hoffmann$^*$},
title = {{FBXO}45-{MYCBP}2 regulates mitotic cell fate by targeting
{FBXW}7 for degradation.},
journal = {Cell death and differentiation},
volume = {27},
number = {2},
issn = {1476-5403},
address = {London},
publisher = {Macmillan},
reportid = {DKFZ-2019-01856},
pages = {758-772},
year = {2020},
note = {2020 Feb;27(2):758-772#EA:F045#LA:F045#},
abstract = {Cell fate decision upon prolonged mitotic arrest induced by
microtubule-targeting agents depends on the activity of the
tumor suppressor and F-box protein FBXW7. FBXW7 promotes
mitotic cell death and prevents premature escape from
mitosis through mitotic slippage. Mitotic slippage is a
process that can cause chemoresistance and tumor relapse.
Therefore, understanding the mechanisms that regulate the
balance between mitotic cell death and mitotic slippage is
an important task. Here we report that FBXW7 protein levels
markedly decline during extended mitotic arrest. FBXO45
binds to a conserved acidic N-terminal motif of FBXW7
specifically under a prolonged delay in mitosis, leading to
ubiquitylation and subsequent proteasomal degradation of
FBXW7 by the FBXO45-MYCBP2 E3 ubiquitin ligase. Moreover, we
find that FBXO45-MYCBP2 counteracts FBXW7 in that it
promotes mitotic slippage and prevents cell death in
mitosis. Targeting this interaction represents a promising
strategy to prevent chemotherapy resistance.},
cin = {F045},
ddc = {610},
cid = {I:(DE-He78)F045-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31285543},
doi = {10.1038/s41418-019-0385-7},
url = {https://inrepo02.dkfz.de/record/144403},
}