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Abstract：
The F-box protein is the substrate recognition subunit of SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase complex, a multicomponent RING-type E3 ligase involved in the regulation of numerous cellular processes by targeting critical regulatory proteins for ubiquitination. However, whether and how F-box proteins are regulated is largely unknown. Here we report that FBXO28, a poorly characterized F-box protein, is a novel substrate of SCF E3 ligase. Pharmaceutical or genetic inhibition of neddylation pathway that is required for the activation of SCF stabilizes FBXO28 and prolongs its half-life. Meanwhile, FBXO28 is subjected to ubiquitination and cullin1-based SCF complex promotes FBXO28 degradation. Moreover, deletion of F-box domain stabilizes FBXO28 and knockdown of endogenous FBXO28 strongly upregulates exogenous FBXO28 expression. Taken together, these data reveal that SCFFBXO28 is the E3 ligase responsible for the self-ubiquitination and proteasomal degradation of FBXO28, providing a new clue for the upstream signaling regulation for F-box proteins.
摘要：
F-box蛋白是SCF（SKP1/CUL1/F-box）E3泛素连接酶复合物的底物识别亚基，一种多组分RING型E3连接酶，通过靶向泛素化的关键调节蛋白参与许多细胞过程的调节。然而,是否以及如何调节F-box蛋白在很大程度上是未知的。在这里，我们报道了FBXO28，一种表征不佳的F-box蛋白，是SCFE3连接酶的新型底物。SCF活化所需的neddylation途径的药物或遗传抑制稳定FBXO28并延长其半衰期。同时,FBXO28经受泛素化,并且基于cullin1的SCF复合物促进FBXO28降解。此外，F-box结构域的缺失稳定了FBXO28,而内源性FBXO28的敲低强烈上调了外源性FBXO28的表达。一起来看,这些数据表明,SCFFBXO28是负责FBXO28自身泛素化和蛋白酶体降解的E3连接酶,为F-box蛋白的上游信号调节提供了新的线索.
