Woods C, LeFeuvre C, Stewart N, Bacchetti S
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Oncogene. 1994 Oct;9(10):2943-50.
Genomic instability is an early event in the transformation of human cells by SV40 and may contribute, as a mutagenic process, to the generation of the rare cells which survive crisis and yield immortal populations. We have previously reported that expression of large T antigen is responsible for induction of chromosome aberrations and aneuploidy. In the present study we have demonstrated that the amino terminal 147 amino acids of the protein are as proficient as full length T antigen for this destabilization of the cell genome. Analysis of mutants within this region indicated that T antigens defective for binding to pRB or lacking the first 127 amino acids are significantly reduced in their ability to induce aneuploidy and/or aberrations, whereas a cytoplasmic T antigen is less severely impaired. In addition, we have shown that binding of T antigen to p53 is dispensable for genome destabilization but may be required for continued proliferation of genetically aberrant cells.
基因组不稳定是SV40转化人类细胞过程中的早期事件，作为一种诱变过程，可能有助于产生在危机中存活并产生永生群体的稀有细胞。我们之前曾报道，大T抗原的表达是诱导染色体畸变和非整倍体的原因。在本研究中，我们证明该蛋白的氨基末端147个氨基酸在使细胞基因组不稳定方面与全长T抗原一样有效。对该区域内突变体的分析表明，与pRB结合有缺陷或缺少前127个氨基酸的T抗原诱导非整倍体和/或畸变的能力显著降低，而细胞质T抗原的受损程度较轻。此外，我们还表明，T抗原与p53的结合对于基因组不稳定并非必需，但可能是遗传异常细胞持续增殖所必需的。
