Mullin M, Lightfoot K, Clarke R, Miller M, Lahesmaa R, Cantrell D
Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, Canada.
FEBS Lett. 2007 Sep 4;581(22):4309-17. doi: 10.1016/j.febslet.2007.07.077. Epub 2007 Aug 10.
The GTPase RhoA is essential for the development of pre-T cells in the thymus. To investigate the mechanisms used by RhoA to control thymocyte development we have used Affymetrix gene profiling to identify RhoA regulated genes in T cell progenitors. The data show that RhoA plays a specific and essential role in pre-T cells because it is required for the expression of transcription factors of the Egr-1 and AP-1 families that have critical functions in thymocyte development. Loss of RhoA function in T cell progenitors causes a developmental block that pheno-copies the consequence of losing pre-TCR expression in Recombinase gene 2 (Rag2) null mice. Transcriptional profiling reveals both common and unique gene targets for RhoA and the pre-TCR indicating that RhoA participates in the pre-TCR induced transcriptional program but also mediates pre-TCR independent gene transcription.
GTP酶RhoA对胸腺中前T细胞的发育至关重要。为了研究RhoA控制胸腺细胞发育所采用的机制,我们利用Affymetrix基因谱分析来鉴定T细胞祖细胞中RhoA调控的基因。数据表明,RhoA在前T细胞中发挥着特定且必不可少的作用,因为它是Egr-1和AP-1家族转录因子表达所必需的,而这些转录因子在胸腺细胞发育中具有关键功能。T细胞祖细胞中RhoA功能的丧失会导致发育阻滞,其表型与重组酶基因2(Rag2)缺失小鼠中前T细胞受体(pre-TCR)表达缺失的后果相似。转录谱分析揭示了RhoA和pre-TCR的共同及独特基因靶点,表明RhoA参与了pre-TCR诱导的转录程序,但也介导了pre-TCR非依赖性基因转录。