Regeling, AnoukArmata, Heather L.Gallant, JudithJones, Stephen N.Sluss, Hayla Karen2022-08-232022-08-232011-08-012011-01-28Transgenic Res. 2011 Aug;20(4):899-912. Epub 2010 Dec 3. <a href="http://dx.doi.org/10.1007/s11248-010-9468-4">Link to article on publisher's site</a>0962-8819 (Linking)10.1007/s11248-010-9468-4https://hdl.handle.net/20.500.14038/36005p53 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.en-USTumor Suppressor Protein p53Genes, p53Nuclear Localization SignalsCell BiologyJournal Articlehttps://escholarship.umassmed.edu/jones/11750934jones/1