title: GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells.
abstract: Misexpression of the dorsal mesodermal patterning factor goosecoid on the ventral side of amphibian embryos results in inhibition of blood formation in early embryogenesis. To investigate the mechanism of this inhibition, we ectopically expressed goosecoid in erythroleukemia cells. While erythroid differentiation of these cells can be induced by activin, goosecoid expressing cells were unresponsive to activin. We demonstrate an in vitro interaction between the oncogene PU.1, an ets family transcription factor thought to play a role in erythropoiesis, and the goosecoid protein (GSC). Interaction with PU.1 was specific as GSC did not bind to the ets family members, Fli-1 or Ets-2. The ability of goosecoid expressing erythroleukemia cells to differentiate in response to activin was rescued by coexpression of the GSC-binding N-terminal portion of PU.1. The N-terminal portion of PU.1 was co-immunoprecipitated with anti-GSC antibodies as well. The N-terminal domain of PU.1 is the region recognized by the retinoblastoma protein (Rb), a tumor suppressor gene presumably involved in erythroid differentiation. We show that GSC competitively inhibits binding of Rb to PU.1. Our data suggest that the suppression of blood formation by GSC could, at least in part, be mediated by binding to PU.1.
authors.affiliation: Medical Research Center, Kochi Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
authors.forename: M
authors.initials: M
authors.lastname: Tominaga
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: F
authors.initials: F
authors.lastname: Imamura
authors.forename: A
authors.initials: A
authors.lastname: Goldfarb
authors.forename: R
authors.initials: R
authors.lastname: Maki
authors.forename: M
authors.initials: M
authors.lastname: Blum
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
authors.forename: A
authors.initials: A
authors.lastname: Tominaga
mesh_terms: D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004912:Erythrocytes / Q000166:cytology*; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D007265:Inhibins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014982:Xenopus laevis; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D028341:Activins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D007265:Inhibins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497993:Gsc protein, mouse