Jun blockade of erythropoiesis: Role for repression of GATA-1 by HERP2

Academic Article

Abstract

  • Although Jun upregulation and activation have been established as critical to oncogenesis, the relevant downstream pathways remain incompletely characterized. In this study, we found that c-Jun blocks erythroid differentiation in primary human hematopoietic progenitors and, correspondingly, that Jun factors block transcriptional activation by GATA-1, the central regulator of erythroid differentiation. Mutagenesis of c-Jun suggested that its repression of GATA-1 occurs through a transcriptional mechanism involving activation of downstream genes. We identified the hairy-enhancer-of-split- related factor HERP2 as a novel gene upregulated by c-Jun. HERP2 showed physical interaction with GATA-1 and repressed GATA-1 transcriptional activation. Furthermore, transduction of HERP2 into primary human hematopoietic progenitors inhibited erythroid differentiation. These results thus define a novel regulatory pathway linking the transcription factors c-Jun, HERP2, and GATA-1. Furthermore, these results establish a connection between the Notch signaling pathway, of which the HERP factors are a critical component, and the GATA family, which participates in programming of cellular differentiation.
  • Digital Object Identifier (doi)

    Author List

  • Elagib KE; Xiao M; Hussaini IM; Delehanty LL; Palmer LA; Racke FK; Birrer MJ; Shanmugasundaram G; McDevitt MA; Goldfarb AN
  • Start Page

  • 7779
  • End Page

  • 7794
  • Volume

  • 24
  • Issue

  • 17