Data that underlies the RT-qPCR in this paper.

Protein ubiquitination is usually coupled with proteasomal degradation and is crucial in regulating protein quality. The E3 ubiquitin-protein ligase SCF (Skp1-Cullin-F-box) complex directly recognizes the target substrate via interaction between the F-box protein and the substrate. F-box protein is the determinant of substrate specificity. The limited number of identified ubiquitin ligase-substrate pairs is a major bottleneck in the ubiquitination field. Penicillium oxalicum contains many transcription factors, such as BrlA, CreA, XlnR, and Ace1, conserved in filamentous fungi that regulate the fungal development and transcription of (hemi)cellulase genes. Transcription factor Ace1 (also known as SltA) positively correlated with fungal growth and conidiation and negatively correlated with the expression of (hemi)cellulase genes. A ubiquitin ligase-substrate pair, SCFFbx23-Ace1, is identified in P. oxalicum. Most of PoFbx23 is present in free form within the nucleus. A small portion of PoFbx23 associates with Skp1 to form PoFbx23-Skp1 heterodimer or assembles with the three invariable core components (Skp1, Cul1, and Rbx1) of SCF to form the SCFFbx23 complex. Under glucose signal, PoFbx23 absence (Δfbx23) results in decreased transcription levels of the brlA gene which encodes the master regulator for asexual development and six spore pigmentation genes (abrB→abrA→aygB→arpA→arpB→albA) which encode the proteins in the dihydroxynaphthalene-melanin pathway, along with impaired conidiation. Under cellulose signal, transcription levels of (hemi)cellulase genes in the Δfbx23 mutant are significantly upregulated. When PoFbx23 is present, PoAce1 exists as a full-length version and several low-molecular-weight degraded versions. PoAce1 has polyubiquitin modification. Deleting the Pofbx23 gene does not affect Poace1 gene transcription but results in the remarkable accumulation of all versions of the PoAce1 protein. Accumulated PoAce1 protein is a dysfunctional form that no longer binds promoters of the target gene, including the cellulase genes cbh1 and eg1, the hemicellulase gene xyn11A, and the pigmentation-related gene abrB. PoFbx23 acts as a transcriptional coactivator, recognizing and activating PoAce1, allowing the latter to regulate the transcription of target genes with different effects (activating or repressing) under different signals.

蛋白质泛素化（Protein ubiquitination）通常与蛋白酶体降解（proteasomal degradation）偶联，在蛋白质质量调控中发挥关键作用。E3泛素蛋白连接酶（E3 ubiquitin-protein ligase）SCF（Skp1-Cullin-F-box）复合物通过F-box蛋白与底物的相互作用直接识别靶底物，而F-box蛋白是底物特异性的决定因素。目前已鉴定的泛素连接酶-底物对数量有限，是泛素化研究领域的主要瓶颈。
草酸青霉（Penicillium oxalicum）含有多种转录因子，如丝状真菌中保守的BrlA、CreA、XlnR和Ace1，这些转录因子调控真菌发育及（半）纤维素酶基因（(hemi)cellulase genes）的转录。转录因子Ace1（又称SltA）与真菌生长和产孢呈正相关，与（半）纤维素酶基因的表达呈负相关。研究在草酸青霉中鉴定到一组泛素连接酶-底物对：SCF^Fbx23-Ace1。PoFbx23大部分以游离形式存在于细胞核内，小部分与Skp1结合形成PoFbx23-Skp1异二聚体，或与SCF复合物的三个恒定核心组分（Skp1、Cul1、Rbx1）组装形成SCF^Fbx23复合物。
在葡萄糖信号条件下，PoFbx23缺失（Δfbx23）会导致brlA基因（编码无性发育主调控因子）的转录水平下降，同时导致6个孢子色素沉着相关基因（abrB→abrA→aygB→arpA→arpB→albA，这些基因编码二羟基萘-黑色素通路中的蛋白）的转录水平降低，同时产孢能力受损。在纤维素信号条件下，Δfbx23突变体中（半）纤维素酶基因的转录水平显著上调。
当存在PoFbx23时，PoAce1以全长形式以及多种低分子量降解形式存在。PoAce1存在多聚泛素修饰（polyubiquitin modification）。敲除Pofbx23基因不会影响Poace1基因的转录，但会导致PoAce1蛋白所有形式的显著积累。积累的PoAce1蛋白为功能失调形式，无法再结合靶基因的启动子，包括纤维素酶基因cbh1和eg1、半纤维素酶基因xyn11A以及色素沉着相关基因abrB。PoFbx23作为转录共激活因子（transcriptional coactivator），识别并激活PoAce1，使其能够在不同信号条件下对靶基因转录发挥不同调控作用（激活或抑制）。