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dc.contributor.advisor Wang, Xiao-Fan en_US
dc.contributor.author Yong, ST
dc.contributor.author Wang, XF
dc.coverage.spatial United States
dc.date.accessioned 2012-01-10T15:57:17Z
dc.date.issued 2012
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/22761665
dc.identifier PONE-D-11-22003
dc.identifier.citation PLoS One, 2012, 7 (6), pp. e38085 - ?
dc.identifier.uri http://hdl.handle.net/10161/4958
dc.description Dissertation en_US
dc.description.abstract BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.
dc.format.extent e38085 - ?
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0038085
dc.subject Apoptosis
dc.subject Blotting, Western
dc.subject Bone Neoplasms
dc.subject Cell Cycle
dc.subject Cell Proliferation
dc.subject Cyclin-Dependent Kinase Inhibitor p21
dc.subject DNA Replication
dc.subject Flow Cytometry
dc.subject Fluorescent Antibody Technique
dc.subject Humans
dc.subject Molecular Chaperones
dc.subject Osteosarcoma
dc.subject Phosphorylation
dc.subject RNA, Small Interfering
dc.subject Tumor Cells, Cultured
dc.title A novel, non-apoptotic role for Scythe/BAT3: a functional switch between the pro- and anti-proliferative roles of p21 during the cell cycle.
dc.type Journal Article
dc.department Molecular Cancer Biology en_US
duke.embargo.months 24 en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/22761665
pubs.issue 6
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.volume 7
dc.identifier.eissn 1932-6203

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