title: A potential role for NEDD1 and the centrosome in senescence of mouse embryonic fibroblasts.
abstract: Mouse embryonic fibroblasts (MEFs) are commonly grown in cell culture and are known to enter senescence after a low number of passages as a result of oxidative stress. Oxidative stress has also been suggested to promote centrosome disruption; however, the contribution of this organelle to senescence is poorly understood. Therefore, this study aimed to assess the role of the centrosome in oxidative stress induced-senescence using MEFs as a model. We demonstrate here that coincident with the entry of late-passage MEFs into senescence, there was an increase in supernumerary centrosomes, most likely due to centrosome fragmentation. In addition, disrupting the centrosome in early-passage MEFs by depletion of neural precursor cell expressed developmentally downregulated gene 1 (NEDD1) also resulted in centrosomal fragmentation and subsequent premature entry into senescence. These data show that a loss of centrosomal integrity may contribute to the entry of MEFs into senescence in culture, and that centrosomal disruption can cause senescence.
authors.affiliation: Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Manning
authors.forename: S
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence; D018385:Centrosome / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C086844:Nedd1 protein, mouse