F-box 蛋白 Fbxl18 介导促凋亡 SCF 亚基 Fbxl7 的多泛素化和蛋白酶体降解。
F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
机构信息
Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
1] Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA [2] Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
出版信息
Cell Death Dis. 2015 Feb 5;6(2):e1630. doi: 10.1038/cddis.2014.585.
Fbxl7, a subunit of the SCF (Skp-Cul1-F-box protein) complex induces mitotic arrest in cells; however, molecular factors that control its cellular abundance remain largely unknown. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. An FQ motif within Fbxl7 serves as a molecular recognition site for Fbxl18 interaction. Ectopically expressed Fbxl7 induces apoptosis in Hela cells, an effect profoundly accentuated after cellular depletion of Fbxl18 protein or expression of Fbxl7 plasmids encoding mutations at either Lys 109 or within the FQ motif. Ectopic expression of Fbxl18 plasmid-limited apoptosis caused by overexpressed Fbxl7 plasmid. Thus, Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7 that may impact cellular processes involved in cell cycle progression.
Fbxl7 是 SCF（Skp-Cul1-F-box 蛋白）复合物的一个亚基，它能诱导细胞有丝分裂停滞；然而，控制其细胞丰度的分子因素在很大程度上仍是未知的。在这里，我们发现一个孤儿 F -box 蛋白 Fbxl18 可将 Fbxl7 作为多泛素化和蛋白酶体降解的靶标。Fbxl7 中的赖氨酸 109 是 Fbxl18 进行泛素缀合的必需接受位点。Fbxl7 中的 FQ 基序作为 Fbxl18 相互作用的分子识别位点。过表达 Fbxl7 可诱导 Hela 细胞凋亡，而在细胞中 Fbxl18 蛋白耗竭或表达 Fbxl7 质粒中 Lys 109 或 FQ 基序内的突变后，这种效应明显增强。Fbxl18 质粒的过表达限制了由过表达 Fbxl7 质粒引起的细胞凋亡。因此，Fbxl18 通过介导促凋亡蛋白 Fbxl7 的泛素依赖性蛋白酶体降解来调节细胞凋亡，这可能会影响细胞周期进程中涉及的细胞过程。
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