| First Author | Regeling A | Year | 2011 |
| Journal | Transgenic Res | Volume | 20 |
| Issue | 4 | Pages | 899-912 |
| PubMed ID | 21127973 | Mgi Jnum | J:175018 |
| Mgi Id | MGI:5142173 | Doi | 10.1007/s11248-010-9468-4 |
| Citation | Regeling A, et al. (2011) Mice defective in p53 nuclear localization signal 1 exhibit exencephaly. Transgenic Res 20(4):899-912 |
| abstractText | 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. |
