Cell cycle-dependent localization of the proteasome to chromatin
Cell cycle-dependent localization of the proteasome to chromatin
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DOI：
10.1038/s41598-020-62697-2
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发表时间：
2020-04-02
影响因子：
4.6
通讯作者：
Nakayama, Keiichi, I
中科院分区：
文献类型：
--
作者：
Kito, Yuki;Matsumoto, Masaki;Nakayama, Keiichi, I
对包括正常细胞和癌细胞转录在内的核事件的综合理解需要对这些事件背后的蛋白质动力学进行全面和定量的测量。然而，大多数核蛋白的低丰度阻碍了它们的详细功能表征。我们现在已经使用蛋白质组学方法在正常和转化的人类二倍体成纤维细胞中全面量化了核蛋白的丰度。我们发现，与野生型细胞相比，转化细胞核部分的26S蛋白酶体复合物亚基明显下调。核内蛋白酶体丰度似乎与细胞周期进展速率呈负相关，细胞周期的限制与细胞核中蛋白酶体亚基数量的增加有关，这表明核蛋白酶体含量依赖于细胞周期。此外，染色质富集蛋白质组学（ChEP）分析显示，蛋白酶体在静止细胞的染色质部分中富集，并且在转化细胞中与染色质明显分离。因此，我们的研究结果表明，核蛋白酶体向染色质的易位可能通过调节染色质相关转录因子在控制细胞周期和肿瘤发生中发挥重要作用。
An integrative understanding of nuclear events including transcription in normal and cancer cells requires comprehensive and quantitative measurement of protein dynamics that underlie such events. However, the low abundance of most nuclear proteins hampers their detailed functional characterization. We have now comprehensively quantified the abundance of nuclear proteins with the use of proteomics approaches in both normal and transformed human diploid fibroblasts. We found that subunits of the 26S proteasome complex were markedly down-regulated in the nuclear fraction of the transformed cells compared with that of the wild-type cells. The intranuclear proteasome abundance appeared to be inversely related to the rate of cell cycle progression, with restraint of the cell cycle being associated with an increase in the amount of proteasome subunits in the nucleus, suggesting that the nuclear proteasome content is dependent on the cell cycle. Furthermore, chromatin enrichment for proteomics (ChEP) analysis revealed enrichment of the proteasome in the chromatin fraction of quiescent cells and its apparent dissociation from chromatin in transformed cells. Our results thus suggest that translocation of the nuclear proteasome to chromatin may play an important role in control of the cell cycle and oncogenesis through regulation of chromatin-associated transcription factors.