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

Show full item record



Permalink

http://hdl.handle.net/10138/178568

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 . DOI: 10.1038/srep42216

Title: Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development
Author: Laos, M.; Sulg, M.; Herranen, A.; Anttonen, T.; Pirvola, U.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology (-2009)
University of Helsinki, External Funding
University of Helsinki, Institute of Biotechnology
University of Helsinki, Molecular and Integrative Biosciences Research Programme
Date: 2017-02-09
Number of pages: 15
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/178568
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.
Subject: IN-VIVO
SUPPORTING CELLS
MOUSE COCHLEA
DIRECT CONVERSION
HUMAN FIBROBLASTS
CHARGE SYNDROME
P53 ACTIVITY
HAIR-CELLS
STEM-CELLS
MICE
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
srep42216.pdf 3.990Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record