Xie Q, Sanz-Burgos A P, Hannon G J, Gutiérrez C
Centro de Biología 'Molecular Severo Ochoa' (CSIC-UAM), Universidad Autónoma, Cantoblanco, Madrid, Spain.
EMBO J. 1996 Sep 16;15(18):4900-8.
The product of the retinoblastoma susceptibility gene (Rb) controls the passage of mammalian cells through G1 phase. Animal virus oncoproteins interact with the Rb protein via an LXCXE motif and disrupt Rb-E2F complexes, driving cells into S-phase. Recently, we found that the RepA protein of a plant geminivirus contains an LXCXE motif that is essential for its function, a finding that predicts the existence of Rb-related proteins in plant cells. Here we report the isolation of a maize cDNA clone encoding a protein (ZmRb1) which, based on structural and functional studies, is closely related to the mammalian Rb family of growth regulatory proteins. ZmRb1 shows a high degree of amino acid conservation when compared with animal Rb members, particularly in the A/B 'pocket' domain, but ZmRb1 has a shorter N-terminal domain. ZmRb1 forms stable complexes with plant LXCXE-containing proteins, e.g. geminivirus RepA protein. Geminivirus DNA replication is reduced in plant cells transfected with plasmids encoding either ZmRb1 or human p130, a member of the Rb family. This suggests that ZmRb1 controls the G1/S transit in plant cells and is consistent with the fact that geminiviruses need an S-phase environment for DNA replication, as animal DNA tumor viruses do. Our results allow the extension of the Rb family of tumor suppressor proteins to plants and have implications on animal and plant strategies for cell growth control.
视网膜母细胞瘤易感基因(Rb)的产物控制哺乳动物细胞通过G1期。动物病毒癌蛋白通过LXCXE基序与Rb蛋白相互作用,破坏Rb-E2F复合物,促使细胞进入S期。最近,我们发现一种植物双生病毒的RepA蛋白含有一个对其功能至关重要的LXCXE基序,这一发现预示着植物细胞中存在与Rb相关的蛋白。在此,我们报告了一个玉米cDNA克隆的分离,该克隆编码一种蛋白质(ZmRb1),基于结构和功能研究,它与哺乳动物生长调节蛋白的Rb家族密切相关。与动物Rb成员相比,ZmRb1显示出高度的氨基酸保守性,特别是在A/B“口袋”结构域,但ZmRb1的N端结构域较短。ZmRb1与含有植物LXCXE的蛋白形成稳定复合物,例如双生病毒RepA蛋白。在用编码ZmRb1或人类p130(Rb家族成员之一)的质粒转染的植物细胞中,双生病毒DNA复制减少。这表明ZmRb1控制植物细胞中的G1/S转换,并且与双生病毒像动物DNA肿瘤病毒一样需要S期环境进行DNA复制这一事实相一致。我们的结果使得肿瘤抑制蛋白Rb家族扩展到植物,并对动物和植物控制细胞生长的策略具有启示意义。