Biology Department, Maynooth University, Maynooth, Co. Kildare, Ireland.
Department of Molecular Microbiology and Genetics and Göttingen Center for Molecular Biosciences (GZMB), Georg-August-Universität Göttingen, Göttingen, Germany.
PLoS Genet. 2022 Dec 12;18(12):e1010502. doi: 10.1371/journal.pgen.1010502. eCollection 2022 Dec.
Fungal growth and development are coordinated with specific secondary metabolism. This coordination requires 8 of 74 F-box proteins of the filamentous fungus Aspergillus nidulans. F-box proteins recognize primed substrates for ubiquitination by Skp1-Cul1-Fbx (SCF) E3 ubiquitin RING ligases and degradation by the 26S proteasome. 24 F-box proteins are found in the nuclear fraction as part of SCFs during vegetative growth. 43 F-box proteins interact with SCF proteins during growth, development or stress. 45 F-box proteins are associated with more than 700 proteins that have mainly regulatory roles. This corroborates that accurate surveillance of protein stability is prerequisite for organizing multicellular fungal development. Fbx23 combines subcellular location and protein stability control, illustrating the complexity of F-box mediated regulation during fungal development. Fbx23 interacts with epigenetic methyltransferase VipC which interacts with fungal NF-κB-like velvet domain regulator VeA that coordinates fungal development with secondary metabolism. Fbx23 prevents nuclear accumulation of methyltransferase VipC during early development. These results suggest that in addition to their role in protein degradation, F-box proteins also control subcellular accumulations of key regulatory proteins for fungal development.
真菌的生长和发育与特定的次级代谢相协调。这种协调需要丝状真菌构巢曲霉中的 74 种 F-box 蛋白中的 8 种。F-box 蛋白识别被 Skp1-Cul1-Fbx（SCF）E3 泛素连接酶泛素化的初始底物，并通过 26S 蛋白酶体进行降解。在营养生长过程中，24 种 F-box 蛋白作为 SCF 的一部分存在于核部分。在生长、发育或应激过程中，有 43 种 F-box 蛋白与 SCF 蛋白相互作用。有 45 种 F-box 蛋白与 700 多种主要具有调节作用的蛋白质相关。这证实了准确监测蛋白质稳定性是组织多细胞真菌发育的前提。Fbx23 结合了亚细胞定位和蛋白质稳定性控制，说明了 F-box 在真菌发育过程中的调节的复杂性。Fbx23 与表观遗传甲基转移酶 VipC 相互作用，而 VipC 又与真菌 NF-κB 样 velvet 结构域调节剂 VeA 相互作用，从而协调真菌发育与次级代谢。Fbx23 阻止了甲基转移酶 VipC 在早期发育过程中的核积累。这些结果表明，除了在蛋白质降解中的作用外，F-box 蛋白还控制着真菌发育的关键调节蛋白的亚细胞积累。
