溴结构域蛋白Brd4与GTP酶激活蛋白SPA-1结合，调节其活性和亚细胞定位。
Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its activity and subcellular localization.
作者信息
Farina Andrea, Hattori Masakazu, Qin Jun, Nakatani Yoshihiro, Minato Nagahiro, Ozato Keiko
机构信息
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2753, USA.
出版信息
Mol Cell Biol. 2004 Oct;24(20):9059-69. doi: 10.1128/MCB.24.20.9059-9069.2004.
Brd4 is a mammalian protein that contains a double bromodomain. It binds to chromatin and regulates cell cycle progression at multiple stages. By immunopurification and mass spectrometry, we identified a Rap GTPase-activating protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence complementation revealed that Brd4 and SPA-1 interact with each other in the nucleus of living cells. Supporting the functional importance of the interaction, Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1 and Brd4 redirected subcellular localization of the partner and disrupted normal cell cycle progression. These effects were, however, reversed by coexpression of the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G2 is required for cell division. This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway.
Brd4是一种含有双溴结构域的哺乳动物蛋白。它与染色质结合并在多个阶段调节细胞周期进程。通过免疫纯化和质谱分析，我们鉴定出一种Rap GTP酶激活蛋白（GAP），即信号诱导增殖相关蛋白1（SPA-1），作为与Brd4相互作用的一个因子。SPA-1定位于细胞质，在细胞核中的定位程度较低，而Brd4位于细胞核中。双荧光互补显示Brd4和SPA-1在活细胞的细胞核中相互作用。支持这种相互作用的功能重要性的是，Brd4增强了SPA-1的Rap GAP活性。此外，SPA-1和Brd4的异位表达改变了伴侣蛋白的亚细胞定位并破坏了正常的细胞周期进程。然而，这两种蛋白的共表达逆转了这些效应，表明在G2期Brd4和SPA-1之间需要适当的平衡才能进行细胞分裂。这项工作揭示了Brd4与一种GTP酶依赖性促有丝分裂信号通路之间的新联系。
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