Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas.

Abstract

The early B-cell factor (EBF)-associated zinc-finger protein (EBFAZ) binds to and negatively regulates EBF, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and development of the olfactory epithelium. It also binds to SMA- and MAD-related protein 1 (SMAD1) and SMAD4 in response to bone morphogenic protein 2 (BMP2) signaling. It is highly related to ecotropic viral integration site 3 (EVI3), a protein that, like EBFAZ, contains 30 Krüppel-like zinc-finger repeats. In previous studies, we showed that Evi3 is a frequent target of retroviral integration in AKXD27 B-cell lymphomas. Here, we show that EBFAZ is also a frequent target. Integrations at Ebfaz and Evi3 are mutually exclusive, suggesting that they function in the same tumor pathway. Lymphomas with integrations at Ebfaz or Evi3 express the pre-B-cell-specific marker immunoglobulin lambda chain 5, and contain immunoglobulin heavy-chain rearrangements, suggesting that they are blocked at an early B-cell stage. Unlike Evi3, which is expressed at low levels in normal B cells, or Ebfaz, which is not expressed in B cells, both genes are highly expressed following viral integration. Collectively, our results suggest that ectopic expression of Ebfaz can substitute for the upregulated expression of Evi3 in B-cell disease and highlight the importance of this gene family in hematopoietic cancer.

• Authors: Søren Warming, Takeshi Suzuki, Terry P Yamaguchi, Nancy A Jenkins, Neal G Copeland
• Journal: Oncogene (Oncogene) Vol. 23 Issue 15 Pg. 2727-31 (Apr 08 2004) ISSN: 0950-9232 [Print] England
• PMID: 15048087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bmp2 protein, mouse
• Bmp2 protein, rat
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins
• DNA, Complementary
• DNA-Binding Proteins
• Ebfaz protein, mouse
• Immunoglobulin Heavy Chains
• Smad Proteins
• Smad1 Protein
• Smad1 protein, mouse
• Smad4 Protein
• Smad4 protein, mouse
• Smad4 protein, rat
• Trans-Activators
• Transcription Factors
• Transforming Growth Factor beta

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Blotting, Southern
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins (metabolism)
• DNA, Complementary (metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Exons
• Immunoglobulin Heavy Chains (metabolism)
• Lymphoma (metabolism)
• Lymphoma, B-Cell (genetics, metabolism, virology)
• Mice
• Models, Genetic
• Molecular Sequence Data
• Protein Binding
• Retroviridae (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Smad Proteins
• Smad1 Protein
• Smad4 Protein
• Tissue Distribution
• Trans-Activators (metabolism)
• Transcription Factors (genetics, metabolism)
• Transforming Growth Factor beta
• Up-Regulation
• Virus Integration