Lübbert M, Miller C W, Kahan J, Koeffler H P
UCLA Department of Medicine, Division of Hematology/Oncology 90024.
Oncogene. 1989 May;4(5):643-51.
p53 is a nuclear protein associated with cellular transformation and normal cellular proliferation. Some transformed cells have been found to have one or several quantitative or qualitative abnormalities of p53. We studied expression, kinetics, phosphorylation, DNA methylation and chromatin structure of p53 in resting and proliferating untransformed T-lymphocytes and in human T-cell leukemia virus type I transformed T-lymphocytes from the same individuals. p53 expression is indistinguishable in transformed compared to untransformed proliferating T-lymphocytes by: (1) p53 mRNA levels, (2) rate of synthesis and stability of p53 protein, (3) change in protein stability after exposure to an inhibitor of protein synthesis, (4) presence of phosphorylation of the p53 protein. Resting T-lymphocytes from these same individuals did not express p53. No difference in DNA methylation and chromatin structure of the p53 gene was observed in either resting or proliferating untransformed, or virally transformed T-lymphocytes. The gene was fully methylated and resistant to DNAase I over its entire coding region but was demethylated and contained DNAase I hypersensitive sites in a distinct region 5' of the site of initiation of transcription.
p53是一种与细胞转化和正常细胞增殖相关的核蛋白。已发现一些转化细胞存在p53的一种或几种数量或质量异常。我们研究了来自同一供体的静息和增殖的未转化T淋巴细胞以及I型人类T细胞白血病病毒转化的T淋巴细胞中p53的表达、动力学、磷酸化、DNA甲基化和染色质结构。与未转化的增殖T淋巴细胞相比，转化的T淋巴细胞中的p53表达在以下方面无差异：（1）p53 mRNA水平，（2）p53蛋白的合成速率和稳定性，（3）暴露于蛋白质合成抑制剂后蛋白质稳定性的变化，（4）p53蛋白磷酸化的存在情况。来自这些供体的静息T淋巴细胞不表达p53。在静息或增殖的未转化或病毒转化的T淋巴细胞中，均未观察到p53基因的DNA甲基化和染色质结构存在差异。该基因在其整个编码区域完全甲基化且对DNA酶I具有抗性，但在转录起始位点5'的一个不同区域去甲基化并含有DNA酶I超敏位点。
