USP7 Regulates Cytokinesis through FBXO38 and KIF20B
USP7 Regulates Cytokinesis through FBXO38 and KIF20B
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DOI：
10.1038/s41598-019-39368-y
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发表时间：
2019-02-25
影响因子：
4.6
通讯作者：
Frappier, Lori
中科院分区：
文献类型：
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作者：
Georges, Anna;Coyaud, Etienne;Frappier, Lori
已知泛素特异性蛋白酶7（USP 7或HAUSP）通过结合和去泛素化特异性靶蛋白来调节多种细胞过程。为了更全面地了解其相互作用和功能，我们使用亲和纯化结合质谱法来分析USP 7相互作用。这揭示了与FBXO 38（一种表征不佳的F-box蛋白）的新型相互作用。我们表明，USP 7通过保护FBXO 38免受蛋白酶体降解来稳定FBXO 38，这取决于其催化活性。我们使用BioID方法来分析FBXO 38的蛋白质相互作用（和推定功能），揭示了与KIF 20 B的相互作用，KIF 20 B是有效胞质分裂所需的驱动蛋白-6蛋白。FBXO 38显示出独立于SCF复合物的功能，以稳定KIF 20 B。因此，FBXO 38或USP 7的消耗导致KIF 20 B水平和中间体处的KIF 20 B显著降低，这表现为细胞动力学缺陷。此外，与USP 7沉默相关的细胞动力学缺陷通过恢复FBXO 38或KIF 20 B而得到挽救。这些结果表明了通过USP 7和FBXO 38调节胞质分裂的新机制。
The ubiquitin specific protease 7 (USP7 or HAUSP) is known to regulate a variety of cellular processes by binding and deubiquitylating specific target proteins. To gain a more comprehensive understanding of its interactions and functions, we used affinity purification coupled to mass spectrometry to profile USP7 interactions. This revealed a novel interaction with FBXO38, a poorly characterized F-box protein. We showed that USP7 stabilizes FBXO38 dependent on its catalytic activity by protecting FBXO38 from proteasomal degradation. We used a BioID approach to profile the protein interactions (and putative functions) of FBXO38, revealing an interaction with KIF20B, a Kinesin-6 protein required for efficient cytokinesis. FBXO38 was shown to function independently from an SCF complex to stabilize KIF20B. Consequently, depletion of either FBXO38 or USP7 led to dramatic decreases in KIF20B levels and KIF20B at the midbody, which were manifested in cytokinetic defects. Furthermore, cytokinetic defects associated with USP7 silencing were rescued by restoring FBXO38 or KIF20B. The results indicate a novel mechanism of regulating cytokinesis through USP7 and FBXO38.