由正性转录延伸因子P-TEFb及其募集因子Brd4蛋白所组成的复合物，在调控基因转录延伸重启中扮演关键作用，与应激性基因转录表达的调节密切相关。我们新近报道了外界刺激因子对Brd4的应激活化作用，并且证明该活化过程是调控P-TEFb募集以及应激性基因转录表达的关键机制。前期筛查结果提示：Brd4的应激活化涉及组蛋白去乙酰化酶和蛋白磷酸酶两条信号途径的协同作用。本项目拟在前期实验研究的基础上，进一步甑别Brd4应激活化相关信号途径、阐释Brd4应激活化的信号和分子调控机制、探讨该机制在抗肿瘤治疗中的应用价值。有关成果，对于应激生物学的研究，应该具有重要的意义。

The complex consisting of P-TEFb (Positive transcription elongation factor) and its recruitment factor Brd4 (Bromodomain containing protein 4) has been shown to play key role in promoting the transition of pausing elongation to productive elongation and in regulating the transcription of stress-inducible genes. We reported that the extracellular stimulations could induce the activation of Brd4 and that this activation was crucial for Brd4 to recruit P-TEFb for regulating the expression of stress-inducible genes. Our recent screening assay suggested that the collaboration of histone deacetylase (HDAC) and protein phasphatase-dependent signal pathways were required for the activation of Brd4. In this proposal, we plan to further identify the exact proteins in the signal pathways and illustrate the molecular mechanism of the collaborative activation of dual signal pathways, and explore the application potential for targeting the Brd4 activation mechanism in anti-cancer therapy.