Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway
Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway
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DOI：
10.1101/gad.12.10.1415
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发表时间：
1998-05-15
影响因子：
10.5
通讯作者：
Pendergast, AM
中科院分区：
文献类型：
--
作者：
Dai, ZH;Quackenbush, RC;Pendergast, AM
Abl和Src酪氨酸激酶的致癌形式触发Abi蛋白的破坏，Abi蛋白是在成纤维细胞中过表达后拮抗Abl的致癌潜力的Abl相互作用蛋白家族。Abi蛋白的破坏需要酪氨酸激酶活性，并且依赖于泛素-蛋白酶体途径。我们发现，阿比特龙蛋白的降解发生通过Ras独立的途径。值得注意的是，从侵袭性Bcr-Abl阳性白血病患者分离的细胞系和骨髓细胞中Abi蛋白的表达丢失。这些研究结果表明，Abi蛋白的损失可能是Bcr-Abl阳性白血病进展的一个组成部分，并确定了一种新的途径，通过泛素-蛋白酶体途径将激活的非受体蛋白酪氨酸激酶与特定靶蛋白的破坏联系起来。
Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of the Abi proteins, a family of Abl-interacting proteins that antagonize the oncogenic potential of Abl after overexpression in fibroblasts. The destruction of the Abi proteins requires tyrosine kinase activity and is dependent on the ubiquitin-proteasome pathway. We show that degradation of the Abi proteins occurs through a Ras-independent pathway. Significantly, expression of the Abi proteins is lost in cell lines and bone marrow cells isolated from patients with aggressive Bcr-Abl-positive leukemias. These findings suggest that loss of Abi proteins may be a component in the progression of Bcr-Abl-positive leukemias and identify a novel pathway linking activated nonreceptor protein tyrosine kinases to the destruction of specific target proteins through the ubiquitin-proteasome pathway.