International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 93 - EVI3 ENCODES AN EBFAZ-RELATED, KRÜPPEL-LIKE, ZINC FINGER GENE

S Warming
National Cancer Institute

Liu P, Suzuki T, Akagi K, Lindtner S, Pavlakis G,  Jenkins N, Copeland N
National Cancer Institute

Evi3 is a common site of retroviral integration in B-cell lymphomas of AKXD mice.  BLAST searches of Evi3 genomic sequences against the mouse and human databases showed that most viral integrations at Evi3 are located immediately upstream of the first translated exon (exon 2) of a gene encoding a novel zinc finger protein with 30 krüppel-like zinc finger repeats.  Viral integrations at Evi3 upregulate the expression of this gene via promoter sequences present in the viral long terminal repeat.  EVI3 protein is highly related to the early B-cell associated zinc finger protein EBFAZ, and all 30 zinc fingers found in EVI3 are conserved in EBFAZ.  Ebfaz and Evi3 are coexpressed in many cell types, and EVI3, like EBFAZ, is located in the nucleus.  EBFAZ binds to, and negatively regulates, early B cell factor (EBF), a basic helix-loop-helix transcription factor required for B-cell-lineage commitment.  EBFAZ also binds to SMAD1 and SMAD4 in response to BMP2 signaling, which in turn activates the homeobox regulator of Xenopus mesoderm and neural development Xvent-2.  Our results suggest that EVI3, like EBFAZ, is a multi-functional protein that participates in many signaling pathways via its multiple zinc fingers, including pathways essential for B-cell lineage commitment.   Deregulation of these signaling pathways by viral integration likely contributes to B-cell disease.


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