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dc.contributor.authorBurns, David M.
dc.contributor.authorRichter, Joel D.
dc.date2022-08-11T08:09:37.000
dc.date.accessioned2022-08-23T16:37:45Z
dc.date.available2022-08-23T16:37:45Z
dc.date.issued2009-01-15
dc.date.submitted2009-10-15
dc.identifier.citation<p>Genes Dev. 2008 Dec 15;22(24):3449-60. <a href="http://dx.doi.org/10.1101/gad.1697808">Link to article on publisher's site</a></p>
dc.identifier.issn0890-9369 (Print)
dc.identifier.doi10.1101/gad.1697808
dc.identifier.pmid19141477
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39095
dc.description.abstractCytoplasmic polyadenylation element-binding protein (CPEB) stimulates polyadenylation and translation in germ cells and neurons. Here, we show that CPEB-regulated translation is essential for the senescence of human diploid fibroblasts. Knockdown of CPEB causes skin and lung cells to bypass the M1 crisis stage of senescence; reintroduction of CPEB into the knockdown cells restores a senescence-like phenotype. Knockdown cells that have bypassed senescence undergo little telomere erosion. Surprisingly, knockdown of exogenous CPEB that induced a senescence-like phenotype results in the resumption of cell growth. CPEB knockdown cells have fewer mitochondria than wild-type cells and resemble transformed cells by having reduced respiration and reactive oxygen species (ROS), normal ATP levels, and enhanced rates of glycolysis. p53 mRNA contains cytoplasmic polyadenylation elements in its 3' untranslated region (UTR), which promote polyadenylation. In CPEB knockdown cells, p53 mRNA has an abnormally short poly(A) tail and a reduced translational efficiency, resulting in an approximately 50% decrease in p53 protein levels. An shRNA-directed reduction in p53 protein by about 50% also results in extended cellular life span, reduced respiration and ROS, and increased glycolysis. Together, these results suggest that CPEB controls senescence and bioenergetics in human cells at least in part by modulating p53 mRNA polyadenylation-induced translation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19141477&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607074/
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCell Aging
dc.subjectCell Line
dc.subjectCells, Cultured
dc.subjectEnergy Metabolism
dc.subject*Gene Expression Regulation, Developmental
dc.subjectGene Knockdown Techniques
dc.subjectGenes, p53
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMolecular Sequence Data
dc.subjectRNA, Messenger
dc.subjectSequence Alignment
dc.subjectTime Factors
dc.subjectTranscription Factors
dc.subjectmRNA Cleavage and Polyadenylation Factors
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleCPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation
dc.typeJournal Article
dc.source.journaltitleGenes and development
dc.source.volume22
dc.source.issue24
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1912
dc.identifier.contextkey1036655
html.description.abstract<p>Cytoplasmic polyadenylation element-binding protein (CPEB) stimulates polyadenylation and translation in germ cells and neurons. Here, we show that CPEB-regulated translation is essential for the senescence of human diploid fibroblasts. Knockdown of CPEB causes skin and lung cells to bypass the M1 crisis stage of senescence; reintroduction of CPEB into the knockdown cells restores a senescence-like phenotype. Knockdown cells that have bypassed senescence undergo little telomere erosion. Surprisingly, knockdown of exogenous CPEB that induced a senescence-like phenotype results in the resumption of cell growth. CPEB knockdown cells have fewer mitochondria than wild-type cells and resemble transformed cells by having reduced respiration and reactive oxygen species (ROS), normal ATP levels, and enhanced rates of glycolysis. p53 mRNA contains cytoplasmic polyadenylation elements in its 3' untranslated region (UTR), which promote polyadenylation. In CPEB knockdown cells, p53 mRNA has an abnormally short poly(A) tail and a reduced translational efficiency, resulting in an approximately 50% decrease in p53 protein levels. An shRNA-directed reduction in p53 protein by about 50% also results in extended cellular life span, reduced respiration and ROS, and increased glycolysis. Together, these results suggest that CPEB controls senescence and bioenergetics in human cells at least in part by modulating p53 mRNA polyadenylation-induced translation.</p>
dc.identifier.submissionpathoapubs/1912
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages3449-60


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