26S proteasome exhibits endoribonuclease activity controlled by extra-cellular stimuli
26S proteasome exhibits endoribonuclease activity controlled by extra-cellular stimuli
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DOI：
10.4161/cc.9.4.10829
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发表时间：
2010-02-15
期刊：
影响因子：
4.3
通讯作者：
Barlev, Nickolai A.
中科院分区：
文献类型：
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作者：
Kulichkova, Valentina A.;Tsimokha, Anna S.;Barlev, Nickolai A.
26 S蛋白酶体是一种多亚基的蛋白质复合体，参与蛋白质的降解。除了其典型的蛋白水解活性外，蛋白酶体还与最近表征的内切核糖核酸酶（endo-RNAse）活性相关。然而，无论是功能的意义，也不是其调节机制目前已知的。在这篇报道中，我们发现26 S蛋白酶体能够水解多种细胞RNA，包括富含AU的c-myc和c-fos mRNA。这些mRNA的内切核酸降解由26 S蛋白酶体亚基之一PSMA 5（α 5）发挥作用。26 S蛋白酶体的RNA酶活性受各种细胞外信号的不同影响。此外，这种活性有助于K562细胞诱导分化过程中c-myc mRNA的降解过程，并可能受到相邻亚基PSMA 1（α 6）和PSMA 3（α 7）磷酸化的控制。总的来说，本报告中提供的数据表明细胞信号传导途径，26 S蛋白酶体复合物的内切RNA酶活性和细胞RNA代谢之间存在因果关系。
26S proteasome is a large multi-subunit protein complex involved in proteolytic degradation of proteins. In addition to its canonical proteolytic activity, the proteasome is also associated with recently characterized endoribonuclease (endo-RNAse) activity. However, neither functional significance, nor the mechanisms of its regulation are currently known. In this report, we show that 26S proteasome is able to hydrolyze various cellular RNAs, including AU-rich mRNA of c-myc and c-fos. The endonucleolytic degradation of these mRNAs is exerted by one of the 26S proteasome subunits, PSMA5 (alpha 5). The RNAse activity of 26S proteasome is differentially affected by various extra-cellular signals. Moreover, this activity contributes to the process of degradation of c-myc mRNA during induced differentiation of K562 cells, and may be controlled by phosphorylation of the adjacent subunits, PSMA1 (alpha 6) and PSMA3 (alpha 7). Collectively, the data presented in this report suggest a causal link between cell signalling pathways, endo-RNAse activity of the 26S proteasome complex and metabolism of cellular RNAs.