Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Characterization of a novel Ets transcription factor, Elf-1.
Diss Abstr Int [B]; 54(11):5537 1994. Unique Identifier : AIDSLINE ICDB/95606818 Wang C; Univ. of Michigan
Abstract:
In this thesis I describe the cloning and characterization of a novel Ets-related transcription factor, Elf-1. Elf-1 is expressed in cells of lymphoid lineage and is able to bind the Ets-binding site in the transcription regulatory elements of multiple T cell genes, including the IL-2 and the GM-CSF genes and that of the HIV-2 LTR. Since Elf-1 is constitutively expressed in normal T cells, the mechanisms of regulating inducible T cell gene expression via Elf-1 were investigated. The transcription regulatory element of the GM-CSF gene is composed of adjacent binding sites for Elf-1 and AP-1. I identified a nuclear protein complex which is able to bind to this element and is rapidly induced following T cell activation. In vitro mutagenesis experiments demonstrated that both the Elf-1 and AP-1 sites are required for the binding of the inducible nuclear protein complex and for the transcriptional activity of this element in activated T cells. Using antibodies specific for different Ets and AP-1 family members, I have demonstrated that the inducible nuclear protein complex is composed of Elf-1, c-fos, and junB. Elf-1 contains a sequence that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from a patient with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcriptional activation. Overexpression of a phosphorylation-defective form of Rb inhibits Elf-1-dependent transcription during T cell activation. These results demonstrate that the transactivation function of Elf-1 is regulated by protein-protein interactions with Rb and the AP-1 transcription factors. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD94-09832)
Keywords: DNA-Binding Proteins/GENETICS/*METABOLISM Gene Expression Phosphorylation Proto-Oncogene Proteins c-fos/METABOLISM Proto-Oncogene Proteins c-jun/METABOLISM Retinoblastoma Protein/METABOLISM T-Lymphocytes/PHYSIOLOGY Transcription Factor AP-1/METABOLISM Transcription Factors/GENETICS/*METABOLISM THESIS 950430
M9541140
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
