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    Mice defective in p53 nuclear localization signal 1 exhibit exencephaly

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    Authors
    Regeling, Anouk
    Armata, Heather L.
    Gallant, Judith
    Jones, Stephen N.
    Sluss, Hayla Karen
    UMass Chan Affiliations
    Department of Medicine, Division of Endocronology and Metabolism
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2011-08-01
    Keywords
    Tumor Suppressor Protein p53
    Genes, p53
    Nuclear Localization Signals
    Cell Biology
    
    Metadata
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    Link to Full Text
    http://dx.doi.org/10.1007/s11248-010-9468-4
    Abstract
    p53 is a major suppressor of human malignancy. The protein levels and activity are tightly regulated in cells. Early experiments identified nuclear localization signal 1 (NLS1) as a regulator of p53 localization. We have generated mice bearing a mutation in p53 ( NLS1 ), designated p53 ( NLS1 ). Our experiments confirm a role for NLS1 in regulating p53 function. Murine embryonic fibroblasts generated from homozygous p53 ( NLS1 ) animals are partially defective in cell cycle arrest and do not respond to inhibitory signals from oncogenic Ras. In addition, p53-dependent apoptosis is abrogated in thymocytes. Contrary to predicted results, fibroblasts from homozygous p53 ( NLS1 ) animals have a greater rate of proliferation than p53-null cells. In addition, p53 ( NLS1 ) cells are more resistant to UV-induced death. Surprisingly, the homozygous p53 ( NLS1 ) animals exhibit embryonic and peri-natal lethality, with a significant portion of the animals developing exencephaly. Thus, p53 ( NLS1/NLS1 ) embryos exhibit a reduced viability relative to p53-null mice. These studies indicate that the NLS1 is a major regulator of p53 activity in vivo.
    Source
    Transgenic Res. 2011 Aug;20(4):899-912. Epub 2010 Dec 3. Link to article on publisher's site
    DOI
    10.1007/s11248-010-9468-4
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/36005
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1007/s11248-010-9468-4
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