C-ETS GENE EXPRESSION DURING CELL PROLIFERATION AND DIFFERENTIATION

点击翻译按钮获取中文摘要

The ets family of genes encode transcription factors and bind to purine- rich sequences present in transcriptional regulatory regions of cellular and viral promoters/enhancers. The DNA binding domain of the ets protein is highly conserved among different members of the family. The homology is less conserved in the transactivation domain region, suggesting different members of the family may be able to modulate target gene activities differently, depending upon their specific interaction with other transcription factors. To understand the mechanisms involved in the regulation of ets targeted genes, highly conserved DNA binding domain of ETS1 and its mutant form are expressed in Jurkat T-cells. The wild- type ETS1 DNA binding domain (ETS1 C) protein, but not the mutant form, binds to ets binding DNA sequences (EBS) at higher affinity and dissociates more slowly than full-length ETS1 protein. Wild-type ETS1 C, but not mutant, inhibits the EBS linked chloramphenicol acetyl transferase (CAT) reporter gene activities and inhibits the production of IL-2. Antisense RNA is being expressed to block the formation of ETS1 and ETS2 proteins in lymphoid as well as non-lymphoid cells to study their role in cell proliferation.