Structure and expression of human Fli-1 gene

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Ets family members are implicated in retroviral-induced leukemias, with mouse Fli-1 involved in a high percentage of erythroleukemias.
• Fli-1's chromosomal location in mice is syntenic with human chromosome 11q23-24, a region associated with human malignancies.

Purpose of the Study:

• To isolate and characterize the human homologue of the Fli-1 gene.
• To investigate the potential role of human Fli-1 in sarcomas, leukemias, and lymphomas.

Main Methods:

• Isolation of complementary DNA clones for the human Fli-1 gene.
• Nucleotide sequence analysis of the human Fli-1 gene and its encoded protein.
• Analysis of human Fli-1 gene transcript size and expression in various cells.
• Comparative sequence analysis of conserved domains within the Fli-1 gene.

Main Results:

• The human Fli-1 gene encodes a 452-amino acid protein with 80% homology to human erg-2.
• A 3.5-kilobase transcript of the human Fli-1 gene was detected in multiple cell types.
• Sequence analysis revealed two ets homology domains, with the 3' domain crucial for DNA binding and the 5' domain conserved in a subset of ets genes.
• Highly homologous 5'-untranslated regions were observed between mouse and human Fli-1 transcripts.

Conclusions:

• Human Fli-1 shares structural and potential functional similarities with its mouse counterpart.
• The conserved 5'-untranslated region suggests a significant role in post-transcriptional regulation of Fli-1.
• Human Fli-1 is a strong candidate for involvement in human cancers associated with chromosome 11q23-24.