TY - JOUR
T1 - Jun blockade of erythropoiesis
T2 - Role for repression of GATA-1 by HERP2
AU - Elagib, Kamaleldin E.
AU - Xiao, Mang
AU - Hussaini, Isa M.
AU - Delehanty, Lorrie L.
AU - Palmer, Lisa A.
AU - Racke, Frederick K.
AU - Birrer, Michael J.
AU - Shanmugasundaram, Ganapath
AU - McDevitt, Michael A.
AU - Goldfarb, Adam N.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.24.17.7779-7794.2004
DO - 10.1128/MCB.24.17.7779-7794.2004
M3 - Article
C2 - 15314183
AN - SCOPUS:4344604163
SN - 0270-7306
VL - 24
SP - 7779
EP - 7794
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 17
ER -