Oukka Mohamed, Kim Sean T, Lugo Geancarlo, Sun Jenny, Wu Lai-Chu, Glimcher Laurie H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, FXB-2, Boston, MA 02115, USA.
Mol Cell. 2002 Jan;9(1):121-31. doi: 10.1016/s1097-2765(01)00434-8.
The cytokine TNFalpha launches cascades of gene activation that control inflammation and apoptosis through NFkappaB and JNK/SAPK signal transduction pathways. Here we describe a function for the zinc finger transcription factor kappa recognition component (KRC) in regulating patterns of gene activation in response to proinflammatory stimuli. We demonstrate that KRC overexpression inhibits while antisense or dominant-negative KRC enhances NFkappaB-dependent transactivation and JNK phosphorylation and consequently, apoptosis and cytokine gene expression. The effect of KRC is mediated through its interaction with the adaptor protein TRAF2, which intersects both pathways. KRC is a hitherto unrecognized participant in the signal transduction pathway leading from the TNF receptor to gene activation and may play a critical role in inflammatory and apoptotic responses.
细胞因子肿瘤坏死因子α（TNFα）引发基因激活级联反应，通过核因子κB（NFκB）和应激活化蛋白激酶/ c-Jun氨基末端激酶（JNK/SAPK）信号转导途径控制炎症和细胞凋亡。在此，我们描述了锌指转录因子κ识别成分（KRC）在调节响应促炎刺激的基因激活模式中的作用。我们证明，KRC过表达会抑制，而反义或显性负性KRC会增强NFκB依赖性反式激活和JNK磷酸化，进而导致细胞凋亡和细胞因子基因表达。KRC的作用是通过其与衔接蛋白肿瘤坏死因子受体相关因子2（TRAF2）的相互作用介导的，TRAF2与这两条途径都有交集。KRC是从肿瘤坏死因子受体到基因激活的信号转导途径中一个迄今未被认识的参与者，可能在炎症和凋亡反应中起关键作用。
