Kharbanda S, Ren R, Pandey P, Shafman T D, Feller S M, Weichselbaum R R, Kufe D W
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1995 Aug 31;376(6543):785-8. doi: 10.1038/376785a0.
The product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents.
c-abl基因的产物是一种非受体酪氨酸激酶，定位于细胞核和细胞质中。c-Abl的确切功能尚不清楚。在此我们表明，电离辐射可激活c-Abl。使用烷化剂顺铂和丝裂霉素C也获得了类似结果。我们还证明，缺乏c-Abl的细胞在受到电离辐射或烷化剂作用后无法激活Jun激酶（JNK/SAP激酶），而在这些细胞中重新表达c-Abl可恢复该反应。相反，对肿瘤坏死因子的应激反应是通过一种不依赖c-Abl的机制来刺激的。这些发现表明，c-abl参与了对DNA损伤剂的应激反应。
