State Key Laboratory of Rice Biology and Breeding, Institute of Biotechnology, Zhejiang University , Hangzhou, China.
mBio. 2023 Aug 31;14(4):e0149923. doi: 10.1128/mbio.01499-23. Epub 2023 Jul 28.
The histone acetyltransferase general control non-depressible 5 (Gcn5) plays a critical role in the epigenetic landscape and chromatin modification for regulating a wide variety of biological events. However, the post-translational regulation of Gcn5 itself is poorly understood. Here, we found that Gcn5 was ubiquitinated and deubiquitinated by E3 ligase Tom1 and deubiquitinating enzyme Ubp14, respectively, in the important plant pathogenic fungus . Tom1 interacted with Gcn5 in the nucleus and subsequently ubiquitinated Gcn5 mainly at K252 to accelerate protein degradation. Conversely, Ubp14 deubiquitinated Gcn5 and enhanced its stability. In the deletion mutant Δ, protein level of Gcn5 was significantly reduced and resulted in attenuated virulence in the fungus by affecting the mycotoxin production, autophagy process, and the penetration ability. Our findings indicate that Tom1 and Ubp14 show antagonistic functions in the control of the protein stability of Gcn5 via post-translational modification and highlight the importance of Tom1-Gcn5-Ubp14 circuit in the fungal virulence. IMPORTANCE Post-translational modification (PTM) enzymes have been reported to be involved in regulating numerous cellular processes. However, the modification of these PTM enzymes themselves is largely unknown. In this study, we found that the E3 ligase Tom1 and deubiquitinating enzyme Ubp14 contributed to the regulation of ubiquitination and deubiquitination of acetyltransferase Gcn5, respectively, in , the causal agent of Fusarium head blight of cereals. Our findings provide deep insights into the modification of acetyltransferase Gcn5 and its dynamic regulation via ubiquitination and deubiquitination. To our knowledge, this work is the most comprehensive analysis of a regulatory network of ubiquitination that impinges on acetyltransferase in filamentous pathogens. Moreover, our findings are important because we present the novel roles of the Tom1-Gcn5-Ubp14 circuit in fungal virulence, providing novel possibilities and targets to control fungal diseases.
组蛋白乙酰转移酶一般控制不可抑制 5（Gcn5）在表观遗传学景观和染色质修饰中发挥着关键作用，可调节广泛的生物学事件。然而，Gcn5 本身的翻译后调控知之甚少。在这里，我们发现 E3 连接酶 Tom1 和去泛素化酶 Ubp14 分别使 Gcn5 发生泛素化和去泛素化，在重要的植物病原真菌 中。Tom1 在核内与 Gcn5 相互作用，随后主要在 K252 处泛素化 Gcn5，以加速蛋白质降解。相反，Ubp14 去泛素化 Gcn5 并增强其稳定性。在缺失突变体 Δ中，Gcn5 的蛋白水平显著降低，并通过影响真菌毒素产生、自噬过程和穿透能力，导致真菌毒力减弱。我们的研究结果表明，Tom1 和 Ubp14 通过翻译后修饰在控制 Gcn5 的蛋白稳定性方面表现出拮抗作用，并强调了 Tom1-Gcn5-Ubp14 回路在真菌毒力中的重要性。重要性：已报道翻译后修饰（PTM）酶参与调节许多细胞过程。然而，这些 PTM 酶本身的修饰在很大程度上是未知的。在这项研究中，我们发现 E3 连接酶 Tom1 和去泛素化酶 Ubp14 分别有助于调节 中的乙酰转移酶 Gcn5 的泛素化和去泛素化， 是谷物赤霉病的病原体。我们的研究结果深入了解了乙酰转移酶 Gcn5 的修饰及其通过泛素化和去泛素化的动态调节。据我们所知，这是关于丝状病原体中泛素化影响乙酰转移酶的调控网络的最全面分析。此外，我们的研究结果很重要，因为我们提出了 Tom1-Gcn5-Ubp14 回路在真菌毒力中的新作用，为控制真菌病提供了新的可能性和靶标。
