Lebowitz P F, Prendergast G C
The Wistar Institute, Philadelphia, PA 19104, USA.
Cell Adhes Commun. 1998;6(4):277-87. doi: 10.3109/15419069809010787.
RhoB has been implicated in cell growth control, actin regulation, adhesion-dependent viability, and gene expression, but its effector functions are poorly defined. Prenylation is important for the physiological functions of Rho proteins, so to identify RhoB effector functions we identified proteins whose interaction was sensitive to prenylation. Here we report the investigation of one such protein, an ubiquitously expressed transcription factor termed DB1 that was originally cloned as a Tax-activated regulator of the IL3 promoter. The RhoB-binding domain in DB1 was located in a functionally undefined region upstream and separable from its zinc finger DNA binding domain. DB1 interacted strongly with prenylated RhoB but weakly with RhoA and not at all with H-Ras. Functional interaction was supported by the identification of prenylated species of RhoB in the nuclear membrane and in an intranuclear laminar region, where they were available for DB1 association in principle, and by the ability of RhoB to inhibit transcriptional activation by DB1, whereas RhoA or Ras had little or no effect, respectively. The results of this study suggest a novel mechanism by which certain Rho proteins may regulate transcription, through sequestration of a transcription factor.
RhoB与细胞生长控制、肌动蛋白调节、黏附依赖性生存能力及基因表达有关，但其效应器功能仍不清楚。异戊二烯化对Rho蛋白的生理功能很重要，因此为了确定RhoB的效应器功能，我们鉴定了其相互作用对异戊二烯化敏感的蛋白质。在此我们报告了对一种这样的蛋白质的研究，一种广泛表达的转录因子，称为DB1，最初作为Tax激活的IL3启动子调节因子被克隆。DB1中的RhoB结合结构域位于其锌指DNA结合结构域上游一个功能未明的区域，且与之可分离。DB1与异戊二烯化的RhoB强烈相互作用，但与RhoA弱相互作用，与H-Ras则完全不相互作用。核膜和核内板层区域中RhoB异戊二烯化形式的鉴定支持了功能相互作用，原则上在这些区域它们可与DB1结合，并且RhoB能够抑制DB1的转录激活，而RhoA或Ras分别几乎没有影响。本研究结果提示了一种新机制，某些Rho蛋白可能通过隔离转录因子来调节转录。
