Ets-2 interacts with co-repressor BS69 to repress target gene expression

Guo Wei, Alicia Erbe Schaffner, Kimberly M. Baker, Kim C. Mansky, Michael C. Ostrowski

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background: The ETS-family of proteins consists of over 30 members that regulate the growth, differentiation and survival of both normal and tumor cells. How specificity is achieved within this family remains largely unresolved. One mechanism for attaining specificity is through the action of signaling pathways on specific family members. For example, Ets-2 is an activator modulated by ras-dependent phosphorylation of a single residue in the conserved pointed domain of this factor. We hypothesized that phosphorylation of the pointed domain regulates the proteins that can interact with ets-2 in the cell nucleus, resulting in regulation of target genes. Materials and Methods: We used a combination of biochemical, assays, yeast two-hybrid screens and transfection assays to identify and characterize proteins interacting with the pointed domain. Results: BS69, a known co-repressor, was identified in a yeast two hybrid screen as an ets-2 interacting partner. BS69 can interact with ets-2 in vivo and phosphorylation of the ets-2 pointed domain decreased the interaction with BS69 in vitro. In transfection assays, co-expression of ets-2 and BS69 resulted in repression of defined ets-2 target genes. Conclusion: These results support a role for ets-2 as a repressor and indicate that BS69 is required as co-repressor. Phosphorylation of ets-2 may switch its activity from repressor to activator by interfering with formation of the BS69 complex.

Original languageEnglish (US)
Pages (from-to)2173-2178
Number of pages6
JournalAnticancer Research
Volume23
Issue number3 A
StatePublished - May 2003

Keywords

  • BS69
  • Ets-2
  • Gene repression
  • Ras signaling pathway

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