Li Sizheng, Guo Yuan, Zhang Shengpei, Li He
State Key Laboratory of Utilization of Woody Oil Resource, Central South University of Forestry and Technology, Changsha, 410004, China.
Key Laboratory for Non-Wood Forest Cultivation and Conservation of Ministry of Education, Changsha, 410004, China.
Stress Biol. 2025 Jun 12;5(1):41. doi: 10.1007/s44154-025-00237-6.
During interactions, pathogenic fungi are subjected to endoplasmic reticulum (ER) stress from the host plants, resulting in the activation of the unfolded protein response (UPR) pathway. We identified the bZIP transcription factor CfHac1 in C. fructicola, which is a pathogenic organism implicated in a variety of plant diseases, and we found it to be crucial for the ER stress response and pathogenicity. However, the role of CfHac1 in regulating the degradation of ER-associated misfolded proteins remains unclear. In this study, we discovered that the CfHAC1 gene regulates conidial production, appressorium formation, response to ER stress, and pathogenicity through unconventional splicing. Further research revealed that the CfHAC1 gene also affects the ubiquitination of ER-associated misfolded proteins and mediates their degradation. We further identified two ubiquitin ligase genes, CfHRD1 and CfHRD3, that exhibit significant down-regulation in the ΔCfhac1 mutant strain. Subsequent investigations revealed that the CfHAC1 gene affects CfHRD1 and CfHRD3 expression through unconventional splicing, with both genes managing the degradation of ER-associated misfolded proteins via ubiquitination and influencing C. fructicola pathogenicity. Taken together, our results reveal a mechanism by which the transcription factor CfHac1 affects the expression of the ubiquitin ligase genes CfHRD1 and CfHRD3, leading to the ubiquitination and degradation of ER-associated misfolded proteins and pathogenicity. This provides a theoretical basis for the development of novel agents targeting key genes within this pathway.
在相互作用过程中，致病真菌会受到宿主植物内质网（ER）应激的影响，从而导致未折叠蛋白反应（UPR）途径的激活。我们在苹果炭疽病菌中鉴定出bZIP转录因子CfHac1，该病菌是一种与多种植物病害有关的致病生物体，我们发现它对于内质网应激反应和致病性至关重要。然而，CfHac1在调节内质网相关错误折叠蛋白降解中的作用仍不清楚。在本研究中，我们发现CfHAC1基因通过非常规剪接调节分生孢子产生、附着胞形成、对内质网应激的反应以及致病性。进一步研究表明，CfHAC1基因还影响内质网相关错误折叠蛋白的泛素化并介导其降解。我们进一步鉴定出两个泛素连接酶基因CfHRD1和CfHRD3，它们在ΔCfhac1突变菌株中表现出显著下调。随后的研究表明，CfHAC1基因通过非常规剪接影响CfHRD1和CfHRD3的表达，这两个基因均通过泛素化来管理内质网相关错误折叠蛋白的降解并影响苹果炭疽病菌的致病性。综上所述，我们的结果揭示了转录因子CfHac1影响泛素连接酶基因CfHRD1和CfHRD3表达的机制，导致内质网相关错误折叠蛋白的泛素化和降解以及致病性。这为开发针对该途径关键基因的新型药剂提供了理论依据。
