Elimination of the vertebrate Escherichia coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis
Elimination of the vertebrate Escherichia coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis
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DOI：
10.1038/sj.onc.1206287
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发表时间：
2003-03-06
期刊：
影响因子：
8
通讯作者：
Inoue, J
中科院分区：
文献类型：
--
作者：
Gohda, J;Nomura, Y;Inoue, J
大肠杆菌（Escherichia coli，E. Ras样蛋白（ERA）是一种具有RNA结合活性的GTP结合蛋白，近年来在人、小鼠和金鱼草等多种生物中发现。原核ERA的缺失阻断细胞分裂而不影响染色体分离。然而，真核ERA的生理功能在很大程度上是未知的。我们在DT 40细胞中进行了鸡ERA（GdERA）的遗传分析。GdERA的耗尽降低了细胞的生长速率，伴随着凋亡细胞的积累。细胞周期分析表明，GdERA的消除导致细胞停滞在G1期，而不是在M期，这突出了脊椎动物ERA在细胞周期进程中与原核ERA不同的作用。此外，人类ERA（HsERA）挽救了GdERA缺陷细胞的表型，而丧失RNA结合活性的HsERA突变体则没有。这些数据表明，脊椎动物ERA调节G1期进展，通过一个未知的分子机制，这涉及RNA识别ERA。
Homologues of the Escherichia coli (E. colt) Ras-like protein (ERA), a GTP-binding protein with RNA binding activity, have recently been found in various species, including human, mouse, and Antirrhinum majus. Depletion of prokaryotic ERA blocks cell division without affecting chromosome segregation. However, the physiological function of eukaryotic ERA is largely unknown. We have performed a genetic analysis of chicken ERA (GdERA) in DT40 cells. Depletion of GdERA diminished the growth rate of the cells, accompanied by an accumulation of apoptotic cells. The analysis of cell cycle indicates that the elimination of GdERA caused arrest at G1 phase, but not at M phase, which highlights the distinct role of vertebrate ERA in the cell cycle progression compared to prokaryotic ERA. Furthermore, human ERA (HsERA) rescued the phenotype of GdERA-deficient cells, whereas a mutant of HsERA deprived of RNA-binding activity did not. These data suggest that vertebrate ERA regulates the G1 phase progression via an as yet unknown molecular mechanism, which involves RNA recognition by ERA.