图1 哺乳动物与植物细胞核糖体应激及DNA损伤反应途径比较 核糖体蛋白突变或核糖体生物发生缺陷会导致核糖体应激。在哺乳动物细胞中, 核糖体应激和DNA损伤反应均由p53响应。正常情况下, p53与E3泛素连接酶MDM2相互作用, 通过泛素降解途径调控其蛋白稳态; 当核糖体应激发生时, 一部分RPs从核仁中释放出来, 与MDM2的酸性结构域结合, 降低其对p53的作用。p53作为转录因子介导下游细胞周期阻滞、细胞衰老及凋亡。在植物中, 类p53转录因子SOG1被ATM和ATR激活并磷酸化, 参与DNA损伤反应, 但是目前尚无证据表明SOG1在核糖体应激响应中发挥作用。而另一个NAC家族转录因子ANAC082可能参与一定的核糖体应激反应。实线箭头表示正常状态, 虚线箭头表示应激状态。

Figure 1 Comparison of ribosomal stress and DNA damage response pathways between mammalian and plant cells Ribosomal stress can be resulted from mutations in genes encoding ribosomal proteins or defects in ribosome biogenesis. In mammalian cells, both ribosomal stress and DNA damage responses are mediated by p53. Under normal conditions, p53 interacts with E3 ubiquitin ligase MDM2, which regulates its protein homeostasis through ubiquitin degradation pathway; when ribosomal stress occurs, some RPs are released from the nucleolus and bind to the acidic domain of MDM2, leading to reduction of its effect on p53. p53 acts as a transcription factor to mediate downstream cell cycle arrest, cell aging and apoptosis. In plants, SOG1, a p53-like transcription factor that can be activated and phosphorylated by ATM and ATR, is involved in DNA damage response, but no evidence shows its involvement in ribosomal stress response. However, another NAC transcription factor, ANAC082, is reported to be involved in ribosomal stress response. Solid arrow indicates the normal state, the dotted arrows indicate stress state.

图2 核糖体发生及MDN1相关功能 RNA Pol I: RNA聚合酶I; RPSs/RPLs: 核糖体小/大亚基蛋白; ARFs: 生长素响应因子; RBFs: 核糖体组装因子。在核糖体合成过程中, MDN1与PES2作为60S RBFs参与60S亚基的组装。MDN1的MIDAS结构域能够与PES2的UBL结构域相互作用, 在60S核糖体前体即将进入核质时, MDN1通过“机械力”使PES2从60S前体中解离; 当60S亚基出核进入胞质时, MDN1也从中解离。生长素与核糖体生物发生之间存在相互协调机制, 正常情况下, 生长素能通过ARF激活MDN1的表达; 当MDN1功能发生异常时(用红色MDN1*表示), 会造成PIN2蛋白积累量增加, AUX1和PIN1积累量降低, 进而改变生长素在植株中的稳态和分布。因此, 生长素系统可能通过参与核糖体应激响应来调控植物的生长发育。

Figure 2 Ribosome biogenesis and the related function of MDN1 RNA Pol I: RNA polymerase I; RPSs/RPLs: Ribosomal proteins of the small/large subunit; ARFs: Auxin response factors; RBFs: Ribosomes biogenetic factors. In the process of ribosome biogenesis, both MDN1 and PES2 participate in the assembly of 60S subunits as RBFs. The MIDAS domain of MDN1 can interact with the UBL domain of PES2. When the 60S ribosome precursor is about to enter the nucleoplasm, MDN1 uses ‘mechanical force' to dissociate PES2 from the 60S precursor; at the nuclear export checkpoint, MDN1 is also dissociated from the 60S ribosomal particle. There is a coordination mechanism between auxin and ribosome biogenesis. Under normal conditions, auxin activates the expression of MDN1 through ARFs. When MDN1 is dysfunction (indicated by the red MDN1*), the accumulation of PIN2 protein increases while that of AUX1 and PIN1 decreases, probably leading to changes in both homeostasis and distribution of auxin in plants. Therefore, the auxin system may participate in the ribosomal stress response to regulate plant growth and development.