Jackson P, Baltimore D
Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.
EMBO J. 1989 Feb;8(2):449-56. doi: 10.1002/j.1460-2075.1989.tb03397.x.
The two major forms of the c-abl gene differ from their activated counterpart, the v-abl oncogene of the Abelson murine leukemia virus by the replacement of their N-terminal sequences with viral gag sequences. Overexpression of p150c-abl type IV in a retroviral vector similar to Abelson virus does not transform NIH 3T3 fibroblasts, even though it is expressed and myristoylated at levels comparable to pp160v-abl. Members of a nested set of deletion mutations of the N-terminus of c-abl type IV in this expression system will activate abl to transform murine fibroblasts. The smallest of these deletions, delta XB, efficiently transforms lymphoid cells in vitro and causes leukemia in vivo demonstrating that gag sequences are not necessary for abl-induced leukemogenesis. The delta XB mutation defines an N-terminal regulatory domain, which shares a surprising homology with chicken oncogene v-crk and phospholipase C-II. Although overexpression of the myristoylated form of c-abl does not transform cells, it nonetheless has a profound effect on cell growth.
c-abl基因的两种主要形式与其激活的对应物——Abelson鼠白血病病毒的v-abl癌基因不同，其N端序列被病毒gag序列取代。在类似于Abelson病毒的逆转录病毒载体中过表达p150c-abl IV型不会转化NIH 3T3成纤维细胞，尽管它的表达和肉豆蔻酰化水平与pp160v-abl相当。在该表达系统中，c-abl IV型N端的一组嵌套缺失突变体成员将激活abl以转化鼠成纤维细胞。这些缺失中最小的delta XB能在体外有效转化淋巴细胞，并在体内引发白血病，表明gag序列对于abl诱导的白血病发生并非必需。delta XB突变定义了一个N端调节域，它与鸡癌基因v-crk和磷脂酶C-II具有惊人的同源性。尽管肉豆蔻酰化形式的c-abl过表达不会转化细胞，但它对细胞生长仍有深远影响。
