DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-KB and AP-1
DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-KB and AP-1
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DOI：
10.1016/s1097-2765(00)80054-4
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发表时间：
1998-03-01
期刊：
影响因子：
16
通讯作者：
Green, DR
中科院分区：
文献类型：
--
作者：
Kasibhatla, S;Brunner, T;Green, DR
DNA损伤和其他应激诱导的细胞凋亡可通过Pas配体（Fast）的表达及其受体Pas （CD95）的连接进行。我们报道了两个转录因子NF-kappa B和AP-1的激活在依托泊苷、天尼泊苷和紫外线照射诱导的快速表达中起着至关重要的作用。一个不可降解的I κ B突变体可以阻断DNA损伤引起的快速表达和细胞凋亡，但不能阻断Fas连接。这些刺激还诱导应激激活激酶通路（SAPK/JNK），这是最大程度诱导细胞凋亡所必需的。一个1.2 kb的Fast启动子响应DNA损伤，并与p65 Rel或Fos/Jun共表达。相关NF-kappa B和AP-1结合位点的突变消除了这些反应。因此，NF-kappa B和AP-1的激活通过Fast的表达参与了应激诱导的细胞凋亡。
Apoptosis induced by DNA damage and other stresses can proceed via expression of Pas ligand (Fast) and ligation of its receptor, Pas (CD95). We report that activation of the two transcription factors NF-kappa B and AP-1 is crucially involved in Fast expression induced by etoposide, teniposide, and UV irradiation. A nondegradable mutant of I kappa B blocked both Fast expression and apoptosis induced by DNA damage but not Fas ligation. These stimuli also induced the stress-activated kinase pathway (SAPK/JNK), which was required for the maximal induction of apoptosis. A 1.2 kb Fast promoter responded to DNA damage, as well as coexpression with p65 Rel or Fos/Jun. Mutations in the relevant NF-kappa B and AP-1 binding sites eliminated these responses. Thus, activation of NF-kappa B and AP-1 contributes to stress-induced apoptosis via the expression of Fast.