Transient Dephosphorylation of p53 Serine 376 as an Early Response to Ionizing Radiation

Abstract Warters, R. L., Gaffney, D. K., Kramer, G. F., Martinez, J. D. and Cress A. E. Transient Phosphorylation of p53 Serine 376 as an Early Response to Ionizing Radiation. Radiat. Res. 171, 725–734 (2009). In a previous paper we reported that the cytoplasmic sequestered p53 in cells of the SK-N-SH neuroblastoma cell line could be induced to translocate to the nucleus by exposure to ionizing radiation. We have extended these studies to determine the fate of p53 in HCT116 colorectal carcinoma cells where constitutive p53 protein resides in the nucleus. A continuous increase in the nuclear p53 protein was observed in irradiated cells beginning 1 h after irradiation that persisted for 8 h. Surprisingly, immunofluorescence microscopy revealed a transient, rapid and sensitive increase in a radiation-induced nuclear dephosphorylated p53 using antibody PAb421, which detects p53 when serine 376 is dephosphorylated. The PAb421 epitope was detectable after exposure to radiation doses as low as 0.5 cGy and was 10...