Physiological roles of enzymatic activity and posttranslational modifications of circadian regulators

越来越多的证据表明，死亡结构域相关蛋白DAXX在调节凋亡通路中具有多种功能。在这项研究中，我们发现BMAL1是一种重要的昼夜节律调节因子，是一种新的daxx相互作用蛋白。生物钟组成部分的时间关联是建立和维持昼夜节律所必需的。值得注意的是，内源性DAXX和BMAL1之间的相互作用具有昼夜节律性。小干扰RNA （siRNA）介导的内源性DAXX表达沉默和DAXX基因的基因消融影响了哺乳动物细胞中昼夜节律基因的表达幅度。此外，DAXX增强了BMAL1:CLOCK异源二聚体的转录能力，BMAL1:CLOCK是昼夜节律系统中重要的转录激活因子。我们的研究结果揭示了DAXX作为生物钟调节因子的一种新功能。

Accumulating evidence suggests that the death domain-associated protein DAXX has a variety of functions in regulating apoptotic pathways. In this study, we have identified BMAL1, an essential circadian regulator, as a novel DAXX-interacting protein. The temporal association of circadian clock components is required for establishing and maintaining circadian rhythms. Notably, the interaction between endogenous DAXX and BMAL1 showed a circadian rhythmicity. Small interfering RNA (siRNA)-mediated silencing of endogenous DAXX expression and genetic ablation of the Daxx gene affected the amplitude of circadian gene expression in mammalian cells. In addition, DAXX enhanced the transcriptional capacity of the BMAL1:CLOCK heterodimer, a vital transcriptional activator in the circadian system. Our results reveal a novel function for DAXX as a modulator of circadian clock regulation.