Abstract:
:Depletion of DNA replication initiation factors such as CDC7 kinase triggers the origin activation checkpoint in healthy cells and leads to a protective cell cycle arrest at the G1 phase of the mitotic cell division cycle. This protective mechanism is thought to be defective in cancer cells. To investigate how this checkpoint is activated and maintained in healthy cells, we conducted a quantitative SILAC analysis of the nuclear- and cytoplasmic-enriched compartments of CDC7-depleted fibroblasts and compared them to a total cell lysate preparation. Substantial changes in total abundance and/or subcellular location were detected for 124 proteins, including many essential proteins associated with DNA replication/cell cycle. Similar changes in protein abundance and subcellular distribution were observed for various metabolic processes, including oxidative stress, iron metabolism, protein translation and the tricarboxylic acid cycle. This is accompanied by reduced abundance of two karyopherin proteins, suggestive of reduced nuclear import. We propose that altered nucleo-cytoplasmic trafficking plays a key role in the regulation of cell cycle arrest. The results increase understanding of the mechanisms underlying maintenance of the DNA replication origin activation checkpoint and are consistent with our proposal that cell cycle arrest is an actively maintained process that appears to be distributed over various subcellular locations.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Mulvey CM,Tudzarova S,Crawford M,Williams GH,Stoeber K,Godovac-Zimmermann Jdoi
10.1021/pr3010919subject
Has Abstractpub_date
2013-03-01 00:00:00pages
1436-53issue
3eissn
1535-3893issn
1535-3907journal_volume
12pub_type
杂志文章abstract::Deficiency of the sulfide metabolizing protein ETHE1 is the cause of ethylmalonic encephalopathy (EE), an inherited and severe metabolic disorder. To study the molecular effects of EE, we performed a proteomics study on mitochondria from cultured patient fibroblast cells. Samples from six patients were analyzed and re...
journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.5b00733
更新日期:2016-07-01 00:00:00
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journal_title:Journal of proteome research
pub_type: 杂志文章,评审
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.9b00360
更新日期:2019-12-06 00:00:00
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journal_title:Journal of proteome research
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更新日期:2009-01-01 00:00:00
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr2006704
更新日期:2012-02-03 00:00:00
abstract::Equine grass sickness (EGS) is a frequently fatal disease of horses, responsible for the death of 1 to 2% of the U.K. horse population annually. The etiology of this disease is currently uncharacterized, although there is evidence it is associated with Clostridium botulinum neurotoxin in the gut. Prevention is current...
journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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更新日期:2011-04-01 00:00:00
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.5b00474
更新日期:2015-09-04 00:00:00
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.8b00615
更新日期:2019-02-01 00:00:00
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journal_title:Journal of proteome research
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更新日期:2012-06-01 00:00:00
abstract::A major challenge in developing cell therapies is reliable characterization of the cell product at the molecular level. Fresh autologous and passaged human bone marrow enriched for stem and mesenchymal stromal stem cells have been used to regenerate bone. We report the proteome of an innovative autologous human bone m...
journal_title:Journal of proteome research
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更新日期:2009-04-01 00:00:00
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journal_title:Journal of proteome research
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更新日期:2006-09-01 00:00:00
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journal_title:Journal of proteome research
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doi:10.1021/pr400260h
更新日期:2013-06-07 00:00:00
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journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr034094y
更新日期:2004-05-01 00:00:00
abstract::The current technique used for microbial identification in hospitals is matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, it suffers from important limitations, in particular, for closely related species or when the database used for the identification lacks the appr...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.0c00351
更新日期:2021-01-01 00:00:00
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journal_title:Journal of proteome research
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更新日期:2010-11-05 00:00:00
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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更新日期:2014-09-05 00:00:00
abstract::The gut microbiota plays a critical role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Increased fructose consumption and inadequate copper intake are two critical risk factors in the development of NAFLD. To gain insight into the role of gut microbiota, fecal metabolites, obtained from rats exposed...
journal_title:Journal of proteome research
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更新日期:2015-09-04 00:00:00
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journal_title:Journal of proteome research
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更新日期:2017-05-05 00:00:00
abstract::We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that tw...
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更新日期:2014-11-07 00:00:00
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更新日期:2014-12-05 00:00:00
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