An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc.
An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc.
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DOI：
10.1016/s1097-2765(00)80427-x
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发表时间：
2000-02
期刊：
影响因子：
16
通讯作者：
Marcelo A. Wood;S. McMahon;M. Cole
中科院分区：
文献类型：
--
作者：
Marcelo A. Wood;S. McMahon;M. Cole
使用c-Myc反式激活结构域来亲和纯化紧密结合的核蛋白。其中两个蛋白被鉴定为TIP 49和一个新的相关蛋白TIP 48，这两个蛋白在进化中高度保守，并含有ATP酶/解旋酶基序。TIP 49和TIP 48在体内与c-Myc复合，并且结合依赖于致癌活性所必需的c-Myc结构域。TIP 49 ATP酶基序中的错义突变作为c-Myc致癌活性的显性抑制剂，但不抑制正常细胞生长，表明功能性TIP 49蛋白是c-Myc致癌转化的重要介质。TIP 49和TIP 48 ATP酶/解旋酶蛋白代表一类由在不同途径中起作用的转录激活结构域募集的新型辅因子。
The c-Myc transactivation domain was used to affinity purify tightly associated nuclear proteins. Two of these proteins were identified as TIP49 and a novel related protein called TIP48, both of which are highly conserved in evolution and contain ATPase/helicase motifs. TIP49 and TIP48 are complexed with c-Myc in vivo, and binding is dependent on a c-Myc domain essential for oncogenic activity. A missense mutation in the TIP49 ATPase motif acts as a dominant inhibitor of c-Myc oncogenic activity but does not inhibit normal cell growth, indicating that functional TIP49 protein is an essential mediator of c-Myc oncogenic transformation. The TIP49 and TIP48 ATPase/helicase proteins represent a novel class of cofactors recruited by transcriptional activation domains that function in diverse pathways.