生物谷报道：乙酰转移酶Tip60调控转录，涉及DNA的损伤响应。现在，它被发现在小鼠模型中和在人类肿瘤中都具有体内肿瘤抑制活性。研究结果发表在最新一期的《自然》杂志上。
人类Tip60位点（HTATIP）在头部和颈部鳞状细胞癌、乳腺癌和淋巴癌中都经常突变。在组织微阵列上着色的核Tip60在各种不同肿瘤中都丢失了，而且最显著的是在乳腺癌中也丢失了。这项工作表明，要在初发肿瘤细胞中发起一个由致癌基因诱导的DNA损伤响应，Tip60的浓度必需达到临界水平：这一防卫机制的失效可能与p53突变发生协同作用，共同促进肿瘤的发育。
FIGURE 1. Tip60 haplo-insufficiency accelerates Myc-induced lymphomagenesis but does not alleviate the pressure for p53 inactivation.
a, Kaplan–Meier curves showing disease-free survival of E –myc mice of the indicated genotypes. The bar graph reports disease onset in the same groups as average s.d. (**P 0.001,*P 0.05). b,c, Genomic DNA from tumour (T) and normal (N) tail tissue from mice of the indicated genotypes was used for PCR with primers amplifying the wild-type (WT) and knockout (KO) alleles of the gene for p53 (Trp53; b) or ARF (c), as indicated. All tumours in E –mycTrp53+/–Tip60+/– mice (10/10) underwent Trp53 LOH (b and data not shown). As shown in a, these tumours developed slightly faster than in E –mycTip60+/– mice, but at the same rate as in E –mycTrp53+/– mice. Similarly, Arf LOH (c)10 and tumour onset (data not shown) were equivalent in Arf+/– and Arf+/–Tip60+/– backgrounds.
原文出处：
Nature Volume 448 Number 7157
Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response p1063
Chiara Gorrini, Massimo Squatrito, Chiara Luise, Nelofer Syed, Daniele Perna, Landon Wark, Francesca Martinato, Domenico Sardella, Alessandro Verrecchia, Samantha Bennett, Stefano Confalonieri, Matteo Cesaroni, Francesco Marchesi, Milena Gasco, Eugenio Scanziani, Maria Capra, Sabine Mai, Paolo Nuciforo, Tim Crook, John Lough & Bruno Amati
doi:10.1038/nature06055
First paragraph | Full Text | PDF (598K) | Supplementary information
See also: Editor's summary
