2025年1月17日，山东农业大学李传友教授团队在Nature Communications发表题为“A multiprotein regulatory module, MED16–MBR1&2, controls MED25 homeostasis during jasmonate signaling”（多蛋白调节模块MED16-MBR1&2在茉莉酸信号传导过程中控制MED25的稳态）的研究论文。
Mediator25（MED25）被认为是一个信号处理和整合中心，控制茉莉酸（JA）诱导和MYC2依赖的转录输出。更好地理解MED25稳定性的调控无疑将促进我们对JA信号相关转录输出的精确调控的认识。在这里，我们报告了拟南芥MED16通过促进MED25的稳定性来激活JA反应基因的表达。相反，两种同源的E3泛素连接酶，MED25-BINDING RING-H2 PROTIN1（MBR1）和MBR2，通过促进MED25降解来负调控JA反应基因的表达。MED16与MBR1和2竞争结合MED25的von Willebrand因子A（vWF-A）结构域，从而拮抗MBR1和2-介导的MED25体内降解。此外，我们发现MED16促进MYC2和MED25之间激素诱导的相互作用，导致JA反应基因表达的激活。总的来说，我们的发现揭示了一个多蛋白调控模块，该模块能够稳健而紧密地维持MED25的稳态，这决定了JA信号的转录输出强度。
Fig. 1: MED16 interacts with and stabilizes MED25.
Fig. 2: MED16 positively regulates MYC2/MED25-dependent JA signaling.
Fig. 3: MBR1 and MBR2 interact with and promote MED25 poly-ubiquitination.
Fig. 4: Negative regulation of multiple JA responses by MBRs depends on MED25.
Fig. 5: MED16 antagonizes MBRs-mediated MED25 degradation.
Abstract
Mediator25 (MED25) has been ascribed as a signal-processing and -integrating center that controls jasmonate (JA)-induced and MYC2-dependent transcriptional output. A better understanding of the regulation of MED25 stability will undoubtedly advance our knowledge of the precise regulation of JA signaling-related transcriptional output. Here, we report that Arabidopsis MED16 activates JA-responsive gene expression by promoting MED25 stability. Conversely, two homologous E3 ubiquitin ligases, MED25-BINDING RING-H2 PROTEIN1 (MBR1) and MBR2, negatively regulate JA-responsive gene expression by promoting MED25 degradation. MED16 competes with MBR1&2 to bind to the von Willebrand Factor A (vWF-A) domain of MED25, thereby antagonizing the MBR1&2-mediated degradation of MED25 in vivo. In addition, we show that MED16 promotes hormone-induced interactions between MYC2 and MED25, leading to the activation of JA-responsive gene expression. Collectively, our findings reveal a multiprotein regulatory module that robustly and tightly maintains MED25 homeostasis, which determines the strength of the transcriptional output of JA signaling.
文章链接：https://www.nature.com/articles/s41467-025-56041-3
