F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
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DOI：
10.1038/cddis.2014.585
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发表时间：
2015-02-05
影响因子：
9
通讯作者：
Mallampalli RK
中科院分区：
文献类型：
--
作者：
Liu Y;Lear T;Zhao Y;Zhao J;Zou C;Chen BB;Mallampalli RK
Fbxl7 是 SCF（Skp-Cul1-F-box 蛋白）复合物的一个亚基，可诱导细胞有丝分裂停滞；然而，控制其细胞丰度的分子因素仍然很大程度上未知。在这里，我们发现了一种孤儿 F-box 蛋白 Fbxl18，其目标是 Fbxl7 的多泛素化和蛋白酶体降解。 Fbxl7 内的 Lys 109 是 Fbxl18 泛素缀合的重要受体位点。 Fbxl7 内的 FQ 基序充当 Fbxl18 相互作用的分子识别位点。异位表达的 Fbxl7 诱导 Hela 细胞凋亡，在细胞耗尽 Fbxl18 蛋白或表达编码 Lys 109 或 FQ 基序内突变的 Fbxl7 质粒后，这种效应会大大增强。 Fbxl18 质粒的异位表达限制了由过表达的 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，这可能影响细胞周期进展中涉及的细胞过程。
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.