Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases.
Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases.
复制标题
设计单一泛素连接酶来选择性降解所有激活的 ErbB 受体酪氨酸激酶
作者：
询问特定的细胞活动通常需要解剖蛋白质家族赋予的翻译后修饰或功能冗余，这需要更复杂的研究工具，而不是简单地通过基因靶向或RNA干扰消除特定的基因产物。我们已经开发了一种新的方法，该方法涉及工程化单个基于SCF β TrCP的泛素连接酶，该泛素连接酶不仅能够同时靶向整个ErbB受体酪氨酸激酶家族进行泛素化和降解，而且能够选择性地仅招募活化的ErbB。SCF βTrCP泛素连接酶能有效阻断ErbB信号通路，降低乳腺癌细胞的致瘤性，但对非癌乳腺上皮细胞的存活和生长影响不大。因此，工程泛素连接酶提供了一个简单的研究工具，剖析致瘤蛋白质家族的特定性状，并提供了一个快速和可行的手段，扩大药物发现的维度，通过评估蛋白质家族或翻译后修饰作为潜在的药物靶点。
Interrogating specific cellular activities often entails the dissection of posttranslational modifications or functional redundancy conferred by protein families, which demands more sophisticated research tools than simply eliminating a specific gene product by gene targeting or RNA interference. We have developed a novel methodology that involves engineering a single SCF βTrCP-based ubiquitin ligase that is capable of not only simultaneously targeting the entire family of ErbB receptor tyrosine kinases for ubiquitination and degradation, but also selectively recruiting only activated ErbBs. The engineered SCF βTrCP ubiquitin ligase effectively blocked ErbB signaling and attenuated oncogenicity in breast cancer cells, yet had little effect on the survival and growth of non-cancerous breast epithelial cells. Therefore, engineering ubiquitin ligases offers a simple research tool to dissect the specific traits of tumorigenic protein families, and provides a rapid and feasible means to expand the dimensionality of drug discovery by assessing protein families or posttranslational modifications as potential drug targets.
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影响因子：
11.2
作者：
Chen, W;Lee, JW;Fine, HA
通讯作者：
Fine, HA
影响因子：
2.3
作者：
Persons, DA;Mehaffey, MG;Vanin, EF
通讯作者：
Vanin, EF
影响因子：
7.3
作者：
Carraway KL 3rd
通讯作者：
Carraway KL 3rd
DOI：
10.1084/jem.20020047
发表时间：
2002-06-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Panigada M;Porcellini S;Barbier E;Hoeflinger S;Cazenave PA;Gu H;Band H;von Boehmer H;Grassi F
通讯作者：
Grassi F
研究β-连环蛋白在肿瘤发生中的功能的蛋白质敲除策略。
影响因子：
--
作者：
Cong, F;Zhang, JX;Pao, W;Zhou, PB;Varmus, H
通讯作者：
Varmus, H