Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division.
Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division.
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DOI：
10.1083/jcb.200801047
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发表时间：
2008-05-05
期刊：
影响因子：
--
通讯作者：
Philips MR
中科院分区：
文献类型：
--
作者：
Michaelson D;Abidi W;Guardavaccaro D;Zhou M;Ahearn I;Pagano M;Philips MR
Rac1调控多种细胞过程。Rac1C末端的多碱区既是质膜靶向基序又是核定位序列(NLS)。我们发现，NLS是由多碱区域的一个三脯氨酸N-末端贡献的，它是隐蔽的，因为它被相邻半胱氨酸的香叶酰化强烈抑制。亚细胞分离表明，在细胞核内有内源性的rac1，而Triton X-114的分离表明，这个池是异丙烯基化的。细胞周期阻滞剂，稳定表达低水平GFP-rac1的细胞的同步化，以及异步细胞的时间推移显微镜显示，rac1在G2晚期聚集在细胞核中，而在G1早期排除。尽管结构性激活的rac1局限于细胞质抑制细胞分裂，但活化的rac1在细胞核中的结构性表达增加了有丝分裂的比率。这些结果表明，在细胞周期中，rac1在细胞核内循环进出细胞核，从而起到促进细胞分裂的作用。
Rac1 regulates a wide variety of cellular processes. The polybasic region of the Rac1 C terminus functions both as a plasma membrane–targeting motif and a nuclear localization sequence (NLS). We show that a triproline N-terminal to the polybasic region contributes to the NLS, which is cryptic in the sense that it is strongly inhibited by geranylgeranylation of the adjacent cysteine. Subcellular fractionation demonstrated endogenous Rac1 in the nucleus and Triton X-114 partition revealed that this pool is prenylated. Cell cycle–blocking agents, synchronization of cells stably expressing low levels of GFP-Rac1, and time-lapse microscopy of asynchronous cells revealed Rac1 accumulation in the nucleus in late G2 and exclusion in early G1. Although constitutively active Rac1 restricted to the cytoplasm inhibited cell division, activated Rac1 expressed constitutively in the nucleus increased the mitotic rate. These results show that Rac1 cycles in and out of the nucleus during the cell cycle and thereby plays a role in promoting cell division.
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影响因子：
7.8
作者：
Jantsch-Plunger, V;Gonczy, P;Romano, A;Schnabel, H;Hamill, D;Schnabel, R;Hyman, A A;Glotzer, M
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