Title

Mice defective in p53 nuclear localization signal 1 exhibit exencephaly

UMMS Affiliation

Department of Cell Biology; Department of Medicine, Division of Endocronology and Metabolism

Date

8-2011

Document Type

Article

Medical Subject Headings

Tumor Suppressor Protein p53; Genes, p53; Nuclear Localization Signals

Disciplines

Cell Biology

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.

Rights and Permissions

Citation: Transgenic Res. 2011 Aug;20(4):899-912. Epub 2010 Dec 3. Link to article on publisher's site

Related Resources

Link to Article in PubMed