Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-cell proto-oncogene product

Takuro Nakamura, Yukari Yamazaki, Yuriko Saiki, Masatsugu Moriyama, David A. Largaespada, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Evi9 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here we show that Evi9 encodes a novel zinc finger protein with three tissue-specific isoforms: Evi9a (773 amino acids [aa]) contains two C2H2-type zinc finger motifs, a proline-rich region, and an acidic domain; Evi9b (486 aa) lacks the first zinc finger motif and part of the proline-rich region; Evi9c (239 aa) lacks all but the first zinc finger motif. Provital integration sites are located in the first intron of the gene and lead to increased gene expression. Evi9a and Evi9c, but not Evi9b, show transforming activity for NIH 3T3 cells, suggesting that Evi9 is a dominantly acting proto-oncogene. Immunolocalization studies show that Evi9c is restricted to the cytoplasm whereas Evi9a and Evi9b are located in the nucleus, where they form a speckled localization pattern identical to that observed for BCL6, a human B-cell proto-oncogene product. Coimmunoprecipitation and glutathione S- transferase pull-down experiments show that Evi9a and Evi9b, but not Evi9c, physically interact with BCL6, while deletion mutagenesis localized the interaction domains in or near the second zinc finger and POZ domains of Evi9 and BCL6, respectively. These results suggest that Evi9 is a leukemia disease gene that functions, in part, through its interaction with BCL6.

Original languageEnglish
Pages (from-to)3178-3186
Number of pages9
JournalMolecular and cellular biology
Volume20
Issue number9
DOIs
Publication statusPublished - 2000 May
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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