Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-4
pubmed:abstractText
Timely induction of cyclin B1 controls mitotic entry, whereas its proteolysis is essential for mitotic exit. By contrast, cyclin B1 transcription is repressed during G(2) arrest induced by DNA damage. The p38 mitogen-activated protein kinase is involved in the G(2) checkpoint; yet, its impact on cyclin B1 protein levels remains unclear. Here we show that untimely proteolysis of cyclin B1 following p38 activation contributes to G(2) checkpoint. Exposing early G(2) cells to arsenite impeded cyclin B1 protein accumulation, Cdk1 activation, and G(2)-to-M progression. Conversely, cyclin B1 was non-degradable in late G(2) and mitotic cells after arsenite. Cyclin B1 proteolysis was enhanced by arsenite in early G(2) and asynchronous cells. This rapid destruction of cyclin B1 was mediated via the ubiquitin-proteasome pathway probably in a Cdc20 and Cdh1 independent mechanism. Under arsenite, inhibition of p38 activation or depletion of p38alpha suppressed cyclin B1 ubiquitination and proteolysis, while forced expression of MKK6-p38 accelerated these events. Inactivation of p38 in arsenite-treated early G(2) cells allowed G(2)-to-M progression, blocked apoptosis, increased cell viability, and decreased micronucleus formation. Thus, p38 signaling pathway triggering cyclin B1 proteolysis after arsenite may play an important role in connecting G(2) arrest with apoptosis or genome instability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-(4-fluorophenyl)-2-(4-hydroxypheny..., http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease, http://linkedlifedata.com/resource/pubmed/chemical/Arsenites, http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDC2 Protein Kinase, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, Environmental, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 14, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Sodium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligase Complexes, http://linkedlifedata.com/resource/pubmed/chemical/anaphase-promoting complex, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci..., http://linkedlifedata.com/resource/pubmed/chemical/sodium arsenite
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17373649-Apoptosis, pubmed-meshheading:17373649-Arsenites, pubmed-meshheading:17373649-CDC2 Protein Kinase, pubmed-meshheading:17373649-Carcinogens, Environmental, pubmed-meshheading:17373649-Cell Division, pubmed-meshheading:17373649-Cell Line, Tumor, pubmed-meshheading:17373649-Cell Survival, pubmed-meshheading:17373649-Cyclin B, pubmed-meshheading:17373649-Cyclin B1, pubmed-meshheading:17373649-Cycloheximide, pubmed-meshheading:17373649-Enzyme Activation, pubmed-meshheading:17373649-G2 Phase, pubmed-meshheading:17373649-Humans, pubmed-meshheading:17373649-Imidazoles, pubmed-meshheading:17373649-Leupeptins, pubmed-meshheading:17373649-MAP Kinase Signaling System, pubmed-meshheading:17373649-Micronuclei, Chromosome-Defective, pubmed-meshheading:17373649-Mitogen-Activated Protein Kinase 14, pubmed-meshheading:17373649-Mitosis, pubmed-meshheading:17373649-Peptide Hydrolases, pubmed-meshheading:17373649-Phosphorylation, pubmed-meshheading:17373649-Protease Inhibitors, pubmed-meshheading:17373649-Proteasome Endopeptidase Complex, pubmed-meshheading:17373649-Protein Kinase Inhibitors, pubmed-meshheading:17373649-Protein Synthesis Inhibitors, pubmed-meshheading:17373649-Pyridines, pubmed-meshheading:17373649-Sodium Compounds, pubmed-meshheading:17373649-Ubiquitin, pubmed-meshheading:17373649-Ubiquitin-Protein Ligase Complexes
pubmed:year
2007
pubmed:articleTitle
Cyclin B1 proteolysis via p38 MAPK signaling participates in G2 checkpoint elicited by arsenite.
pubmed:affiliation
Molecular Carcinogenesis Laboratory, Institute of Biotechnology and Department of Life Sciences, National Tsing Hua University, Hsinchu, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't