In:
PLOS Biology, Public Library of Science (PLoS), Vol. 18, No. 12 ( 2020-12-11), p. e3000975-
Kurzfassung:
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates, and we show experimentally that several chromatin proteins bind APC/C, oscillate during the cell cycle, and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3000975
DOI:
10.1371/journal.pbio.3000975.g001
DOI:
10.1371/journal.pbio.3000975.g002
DOI:
10.1371/journal.pbio.3000975.g003
DOI:
10.1371/journal.pbio.3000975.g004
DOI:
10.1371/journal.pbio.3000975.g005
DOI:
10.1371/journal.pbio.3000975.g006
DOI:
10.1371/journal.pbio.3000975.g007
DOI:
10.1371/journal.pbio.3000975.s001
DOI:
10.1371/journal.pbio.3000975.s002
DOI:
10.1371/journal.pbio.3000975.s003
DOI:
10.1371/journal.pbio.3000975.s004
DOI:
10.1371/journal.pbio.3000975.s005
DOI:
10.1371/journal.pbio.3000975.s006
DOI:
10.1371/journal.pbio.3000975.s007
DOI:
10.1371/journal.pbio.3000975.s008
DOI:
10.1371/journal.pbio.3000975.s009
DOI:
10.1371/journal.pbio.3000975.s010
DOI:
10.1371/journal.pbio.3000975.s011
DOI:
10.1371/journal.pbio.3000975.s012
DOI:
10.1371/journal.pbio.3000975.s013
DOI:
10.1371/journal.pbio.3000975.s014
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2020
ZDB Id:
2126773-X
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