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.
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.
Authors: Christopher P Baran; Sara N Fischer; Gerard J Nuovo; Mohamed N Kabbout; Charles L Hitchcock; Benjamin D Bringardner; Sara McMaken; Christie A Newland; Carmen Z Cantemir-Stone; Gary S Phillips; Michael C Ostrowski; Clay B Marsh Journal: Am J Respir Cell Mol Biol Date: 2011-05-11 Impact factor: 6.914
Authors: Tahera Zabuawala; David A Taffany; Sudarshana M Sharma; Anand Merchant; Brett Adair; Ruchika Srinivasan; Thomas J Rosol; Soledad Fernandez; Kun Huang; Gustavo Leone; Michael C Ostrowski Journal: Cancer Res Date: 2010-02-09 Impact factor: 12.701
Authors: Ali Zhang; Tanner M Tessier; Kristianne J C Galpin; Cason R King; Steven F Gameiro; Wyatt W Anderson; Ahmed F Yousef; Wen T Qin; Shawn S C Li; Joe S Mymryk Journal: Viruses Date: 2018-11-22 Impact factor: 5.048