Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation
Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation
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DOI：
10.1128/mcb.24.18.8236-8243.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Mizutani, S
中科院分区：
文献类型：
--
作者：
Asada, M;Ohmi, K;Mizutani, S
细胞周期抑制因子p21在单核细胞分化过程中起着重要作用，在此过程中p21从胞核向胞浆转位。这一过程涉及p21核定位信号(NLS)的负调控。在这里，我们试图确定p21的细胞质易位与另一个分子BRap2之间的关系，BRap2是一种细胞质蛋白，与BRCA1的NLS结合，最近被报道以IMP的名义在RAS激活信号通路中使KSR失活。我们报道了p21和BRap2在体外和体内直接相互作用的方式，需要p21的NLS和BRap2的C-末端部分。当p21与BRap2共转染时，p21在细胞质中表达。早幼粒单核细胞系U937和HL60的单核细胞分化与BRap2表达上调有关，同时伴随着p21的上调和胞浆再定位。我们的结果强调了BRap2在单核细胞分化过程中p21的胞浆转位过程中所起的作用。
The cell cycle inhibitor p21 plays an important role in monocytic cell differentiation, during which it translocates from the nucleus to cytoplasm. This process involves the negative regulation of the p21 nuclear localization signal (NLS). Here, we sought to determine the relationship between the cytoplasmic translocation of p21 and another molecule, Brap2, a cytoplasmic protein which binds the NLS of BRCA1 and was recently reported to inactivate KSR in the Ras-activating signal pathway under the name of IMP. We report that p21 and Brap2 directly interact, both in vitro and in vivo, in a manner requiring the NLS of p21 and the C-terminal portion of Brap2. When it is cotransfected with Brap2, p21 is expressed in the cytoplasm. Monocytic differentiation of the promyelomonocytic cell lines U937 and HL60 is associated with the upregulation of Brap2 expression concomitantly with the upregulation and cytoplasmic rellocalization of p21. Our results underscore the role played by Brap2 in the process of cytoplasmic translocation of p21 during monocyte differentiation.