IKKα通过不同机制介导生长促进和生长抑制信号诱导的c-Fos表达和AP-1活化  

IKKα Mediates c-Fos Induction and AP-1 Transactivation via Different Mechanism Under Cell Proliferative or Growth Arrest Conditions

作　　者：王红丽[1,2] 李译[1,3] 董雯[1] 胡美茹[4] 马远方[2] 郭宁[5] 宋伦[1] 

机构地区：[1]军事医学科学院基础医学研究所应激医学研究室,北京100850 [2]河南大学医学院细胞与分子免疫学实验室,河南开封475004 [3]中国药科大学新药筛选中心,江苏南京210009 [4]军事医学科学院 基础医学研究所应激医学研究室,北京100850 [5]军事医学科学院基础医学研究所军事认知科学研究室,北京100850

出　　处：《生物技术通讯》2014年第5期636-639,共4页Letters in Biotechnology

基　　金：国家自然科学基金(31171342;31270797);国家重点基础研究发展计划(2011CB503803)

摘　　要：目的:探讨IKK激酶催化亚基IKKα在分别介导生长促进信号(血清)和生长抑制信号(紫外线UVB)诱导的反应中,调控转录因子AP-1关键组成亚基c-Fos实现诱导表达的信号传递机制。方法:分别采用Western印迹、RT-PCR和萤光素酶报道分析系统检测血清和紫外线刺激反应状态下IKKα对c-Fos诱导表达和AP-1诱导活化的调控作用;通过转染I-κBα功能抑制型突变体I-κBα-AA,观察NF-κB诱导活化受抑时,c-Fos诱导表达和AP-1诱导活化水平的改变情况。结果:IKKα在生长促进和生长抑制信号诱导的反应中,都能够实现对转录因子AP-1及其关键组成亚基c-Fos诱导表达的调控作用。其中,在血清反应中IKKα可通过NF-κB依赖方式在转录水平调控c-Fos的诱导表达,而在UVB反应中IKKα通过转录非依赖方式调控c-Fos的诱导表达。结论:IKKα能分别以NF-κB依赖和非依赖方式参与调控生长促进和生长抑制信号诱导的反应。Objective： To figure out the mechanism of IKKα, catalytic subunit of IKK complex, in regulating the induction of c-Fos expression and AP-1 transactivation under serum-induced cell proliferative or UVB-induced growth arrest conditions. Methods： The regulatory role of IKKα in regulating c-Fos expression and AP-1 transactivation was determined by western-blot, RT-PCR and luciferase reporter assays, respectively. The dominant negative mutant of I-KBα, I-KBα-AA, was used to detect whether c-Fos induction depends on NF-KB. Results： IKKα played important roles in both serum and UVB-induced c-Fos expression and AP-1 transactivation. Howev- er, IKKα-mediated c-Fos induction occurred at the transcriptional level and was dependent on NF-KB transactivation in the serum-induced response; while c-Fos induction occurred at the post-translational level and was unrelated to NF-KB transactivation in the UVB-induced response. Conclusion： IKKα is involved in serum-induced cell proliferative or UVB-induced growth arrest responses via NF-KB-dependent or independent manner.

关 键 词：IKKα NF-ΚB C-FOS表达 AP-1活化 

分 类 号：Q255[生物学—细胞生物学]