دورية أكاديمية

In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators.

التفاصيل البيبلوغرافية
العنوان: In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators.
المؤلفون: Franks JL; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Martinez-Chacin RC; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Wang X; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Tiedemann RL; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, United States of America., Bonacci T; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Choudhury R; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Bolhuis DL; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Enrico TP; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Mouery RD; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Damrauer JS; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Yan F; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Harrison JS; Department of Chemistry, University of the Pacific, Stockton, California, United States of America., Major MB; Department of Cell Biology and Physiology, Department of Otolaryngology, Washington University in St. Louis, St. Louis, Missouri, United States of America., Hoadley KA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Suzuki A; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, Wisconsin, United States of America., Rothbart SB; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, United States of America., Brown NG; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Emanuele MJ; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
المصدر: PLoS biology [PLoS Biol] 2020 Dec 11; Vol. 18 (12), pp. e3000975. Date of Electronic Publication: 2020 Dec 11 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2003]-
مواضيع طبية MeSH: Anaphase-Promoting Complex-Cyclosome/*metabolism , CCAAT-Enhancer-Binding Proteins/*metabolism , Chromatin/*metabolism , Ubiquitin-Protein Ligases/*metabolism, Anaphase-Promoting Complex-Cyclosome/physiology ; CCAAT-Enhancer-Binding Proteins/genetics ; CCAAT-Enhancer-Binding Proteins/physiology ; Cell Cycle/physiology ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromatin/genetics ; Computer Simulation ; HEK293 Cells ; HeLa Cells ; Humans ; Protein Processing, Post-Translational ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/physiology ; Ubiquitination
مستخلص: 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.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: NGB is a consultant for Cullgen, Inc.
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معلومات مُعتمدة: P30 CA016086 United States CA NCI NIH HHS; T32 GM007040 United States GM NIGMS NIH HHS; R01 GM120309 United States GM NIGMS NIH HHS; T32 CA071341 United States CA NCI NIH HHS; R35 GM128855 United States GM NIGMS NIH HHS; R35 GM124736 United States GM NIGMS NIH HHS; R01 GM134231 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (CCAAT-Enhancer-Binding Proteins)
0 (Cell Cycle Proteins)
0 (Chromatin)
0 (Transcription Factors)
EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
EC 2.3.2.27 (UHRF1 protein, human)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
تواريخ الأحداث: Date Created: 20201211 Date Completed: 20210202 Latest Revision: 20210630
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7758050
DOI: 10.1371/journal.pbio.3000975
PMID: 33306668
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-7885
DOI:10.1371/journal.pbio.3000975