Dai Z, Quackenbush R C, Courtney K D, Grove M, Cortez D, Reuther G W, Pendergast A M
Department of Pharmacology and Cancer Biology and Division of Hematology-Oncology, Duke University Medical Center, Durham, North Carolina 27710,
Genes Dev. 1998 May 15;12(10):1415-24. doi: 10.1101/gad.12.10.1415.
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.
Abl和Src酪氨酸激酶的致癌形式会引发Abi蛋白的降解，Abi蛋白是一类与Abl相互作用的蛋白，在成纤维细胞中过表达后可拮抗Abl的致癌潜力。Abi蛋白的降解需要酪氨酸激酶活性，且依赖于泛素-蛋白酶体途径。我们发现Abi蛋白的降解是通过一条不依赖Ras的途径发生的。值得注意的是，在从侵袭性Bcr-Abl阳性白血病患者分离出的细胞系和骨髓细胞中，Abi蛋白的表达缺失。这些发现表明，Abi蛋白的缺失可能是Bcr-Abl阳性白血病进展的一个因素，并确定了一条新的途径，该途径通过泛素-蛋白酶体途径将活化的非受体蛋白酪氨酸激酶与特定靶蛋白的降解联系起来。
