THE ONCOGENIC POTENTIAL OF PAX GENES
THE ONCOGENIC POTENTIAL OF PAX GENES
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DOI：
10.1002/j.1460-2075.1993.tb05890.x
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发表时间：
1993-06-01
期刊：
影响因子：
11.4
通讯作者：
GRUSS, P
中科院分区：
文献类型：
--
作者：
MAULBECKER, CC;GRUSS, P
我们的研究结果表明，小鼠配对结构域的基因（Pax）可以促进肿瘤发生在组织培养细胞和小鼠，因此应被归类为一组新的原癌基因。小鼠肿瘤形成的诱导依赖于功能配对结构域，但不需要同源结构域的存在。因此，不仅Pax-3和Pax-6蛋白（其除了配对结构域之外还含有完整的同源结构域），而且Pax-2和Pax-8（其仅含有残留的同源结构域）以及Pax-1（其完全缺乏同源结构域）都能够诱导小鼠中细胞培养物的转化和肿瘤形成。Pax蛋白的致癌潜力取决于配对基序的DNA结合功能，因为在该结构域中携带损害DNA结合的点突变的Un-Pax-1蛋白在肿瘤形成中也有缺陷。因此，Pax基因产物不仅参与控制胚胎发生，而且如果失调，它们也可以诱导肿瘤发生。
Our results demonstrate that murine paired domain-containing genes (Pax) can promote oncogenesis in tissue culture cells and in mice, and should thus be classified as a novel group of proto-oncogenes. The induction of tumor formation in mice was dependent on a functional paired domain, but did not require the presence of a homeodomain. Consequently, not only the Pax-3 and Pax-6 proteins, which in addition to paired domains contain intact homeodomains,but also Pax-2 and Pax-8, containing only residual homeodomains, and Pax-1, completely lacking a homeodomain, were able to induce transformation of cell cultures and tumor formation in mice. The oncogenic potential of the Pax proteins is dependent on the DNA binding function of the paired motif, as the Un-Pax-1 protein, which carries a point mutation in this domain that impairs DNA binding, is also defective in tumor formation. Therefore, the Pax gene products are not only involved in controlling embryogenesis, but they can, if deregulated, also induce tumorigenesis.