Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development

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dc.contributor University of Helsinki, Finnish Museum of Natural History en
dc.contributor University of Helsinki, Biosciences en
dc.contributor University of Helsinki, Biosciences en
dc.contributor University of Helsinki, Biosciences en
dc.contributor University of Helsinki, Biosciences en
dc.contributor.author Laos, M.
dc.contributor.author Sulg, M.
dc.contributor.author Herranen, A.
dc.contributor.author Anttonen, T.
dc.contributor.author Pirvola, U.
dc.date.accessioned 2017-03-27T12:44:01Z
dc.date.available 2017-03-27T12:44:01Z
dc.date.issued 2017-02-09
dc.identifier.citation Laos , M , Sulg , M , Herranen , A , Anttonen , T & Pirvola , U 2017 , ' Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development ' , Scientific Reports , vol. 7 , 42216 . https://doi.org/10.1038/srep42216 en
dc.identifier.issn 2045-2322
dc.identifier.other PURE: 82081969
dc.identifier.other PURE UUID: cac3bc4c-9dc9-44c9-bb8e-43a4422aadc6
dc.identifier.other WOS: 000393562500001
dc.identifier.other Scopus: 85012066926
dc.identifier.other ORCID: /0000-0002-6341-6842/work/31552342
dc.identifier.uri http://hdl.handle.net/10138/178568
dc.description.abstract p53 is a key component of a signaling network that protects cells against various stresses. As excess p53 is detrimental to cells, its levels are tightly controlled by several mechanisms. The E3 ubiquitin ligase Mdm2 is a major negative regulator of p53. The significance of balanced p53 levels in normal tissues, at different stages of lifetime, is poorly understood. We have studied in vivo how the disruption of Mdm2/p53 interaction affects the early-embryonic otic progenitor cells and their descendants, the auditory supporting cells and hair cells. We found that p53 accumulation, as a consequence of Mdm2 abrogation, is lethal to both proliferative progenitors and non-proliferating, differentiating cells. The sensitivity of postmitotic supporting cells to excess p53 decreases along maturation, suggesting that maturation-related mechanisms limit p53's transcriptional activity towards pro-apoptotic factors. We have also investigated in vitro whether p53 restricts supporting cell's regenerative capacity. Unlike in several other regenerative cellular models, p53 inactivation did not alter supporting cell's proliferative quiescence nor transdifferentiation capacity. Altogether, the postmitotic status of developing hair cells and supporting cells does not confer protection against the detrimental effects of p53 upregulation. These findings might be linked to auditory disturbances observed in developmental syndromes with inappropriate p53 upregulation. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights en
dc.subject IN-VIVO en
dc.subject SUPPORTING CELLS en
dc.subject MOUSE COCHLEA en
dc.subject DIRECT CONVERSION en
dc.subject HUMAN FIBROBLASTS en
dc.subject CHARGE SYNDROME en
dc.subject P53 ACTIVITY en
dc.subject HAIR-CELLS en
dc.subject STEM-CELLS en
dc.subject MICE en
dc.subject 1182 Biochemistry, cell and molecular biology en
dc.title Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/srep42216
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
dc.contributor.pbl
dc.contributor.pbl

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