Hallahan D E, Sukhatme V P, Sherman M L, Virudachalam S, Kufe D, Weichselbaum R R
Department of Radiation and Cellular Oncology, Howard Hughes Medical Institute, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2156-60. doi: 10.1073/pnas.88.6.2156.
The cellular response to ionizing radiation includes growth arrest and DNA repair followed by proliferation. Induction of immediate early response genes may participate in signal transduction preceding these phenotypic responses. We analyzed mRNA expression for different classes of immediate early genes (JUN, EGR1, and FOS) after cellular x-irradiation. Increased expression of the EGR1 and JUN genes was observed within 0.5-3 hr following x-ray exposure. Preincubation with cycloheximide was associated with superinduction of JUN and EGR1 in x-irradiated cells. Inhibition of protein kinase C activity by prolonged stimulation with phorbol 12-myristate 13-acetate or the protein kinase inhibitor H7 prior to irradiation attenuated the increase in EGR1 and JUN transcripts. FOS expression was not coregulated with that of EGR1 following x-irradiation, suggesting a distinct regulatory pathway of this gene as compared with its regulation following serum and phorbol ester. These data implicate the EGR1 and JUN proteins as signal transducers during the cellular response to radiation injury and suggest that this effect is mediated in part by a protein kinase C-dependent pathway.
细胞对电离辐射的反应包括生长停滞、DNA修复，随后是增殖。立即早期反应基因的诱导可能参与这些表型反应之前的信号转导。我们分析了细胞X线照射后不同类别的立即早期基因（JUN、EGR1和FOS）的mRNA表达。在X线照射后0.5 - 3小时内观察到EGR1和JUN基因表达增加。用环己酰亚胺预孵育与X线照射细胞中JUN和EGR1的超诱导有关。在照射前用佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯长时间刺激或用蛋白激酶抑制剂H7抑制蛋白激酶C活性可减弱EGR1和JUN转录本的增加。X线照射后FOS的表达与EGR1的表达没有共同调节，这表明与血清和佛波酯刺激后相比，该基因有独特的调节途径。这些数据表明EGR1和JUN蛋白在细胞对辐射损伤的反应中作为信号转导分子，并且表明这种作用部分是由蛋白激酶C依赖性途径介导的。
