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

Kamaleldin E. Elagib, Mang Xiao, Isa M. Hussaini, Lorrie L. Delehanty, Lisa A. Palmer, Frederick K. Racke, Michael J. Birrer, Ganapath Shanmugasundaram, Michael A. McDevitt, Adam N. Goldfarb

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)7779-7794
Number of pages16
JournalMolecular and cellular biology
Volume24
Issue number17
DOIs
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Elagib, K. E., Xiao, M., Hussaini, I. M., Delehanty, L. L., Palmer, L. A., Racke, F. K., Birrer, M. J., Shanmugasundaram, G., McDevitt, M. A., & Goldfarb, A. N. (2004). Jun blockade of erythropoiesis: Role for repression of GATA-1 by HERP2. Molecular and cellular biology, 24(17), 7779-7794. https://doi.org/10.1128/MCB.24.17.7779-7794.2004