Bories J C, Willerford D M, Grévin D, Davidson L, Camus A, Martin P, Stéhelin D, Alt F W
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature. 1995 Oct 19;377(6550):635-8. doi: 10.1038/377635a0.
The Ets-1 proto-oncogene is a member of a transcription factor family characterized by homology to the v-ets oncogene. In adult mice, Ets-1 is expressed predominantly in lymphoid cells where it has been implicated in regulating transcription of lymphocyte-specific genes. Following T-cell activation, the specific DNA binding activity of Ets-1 is inactivated by transient phosphorylation, suggesting a function in the transition from the resting to activated state. Ets-1 has also been suggested to cooperate with the AP-1 transcription factor complex to mediate cellular growth factor responses. Here we show, by using RAG-2-deficient blastocyst complementation, that Ets-1 deficiency has dramatic, but different, effects on development and function of T- and B-lineage cells. Ets-1-deficient T cells were present in reduced numbers and were highly susceptible to cell death in vitro. In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal pool of resting T- and B-lineage cells.
Ets-1原癌基因是转录因子家族的成员，其特征在于与v-ets癌基因具有同源性。在成年小鼠中，Ets-1主要在淋巴细胞中表达，在那里它参与调节淋巴细胞特异性基因的转录。T细胞活化后，Ets-1的特异性DNA结合活性通过瞬时磷酸化而失活，这表明其在从静止状态到活化状态的转变中发挥作用。也有研究表明Ets-1与AP-1转录因子复合物协同作用以介导细胞生长因子反应。在这里，我们通过使用RAG-2缺陷型囊胚互补实验表明，Ets-1缺陷对T细胞和B细胞系细胞的发育和功能具有显著但不同的影响。Ets-1缺陷的T细胞数量减少，并且在体外极易发生细胞死亡。相反，Ets-1缺陷的B细胞数量正常，但很大一部分是IgM浆细胞。我们的数据表明，Ets-1对于维持静止的T细胞和B细胞系细胞的正常库至关重要。
