|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3369-3378
Regulated Expression and Functional Role of the Transcription Factor
CHOP (GADD153) in Erythroid Growth and Differentiation
Margaret Coutts,
Kunyuan Cui,
Kerry L. Davis,
Joan Cleves Keutzer, and
Arthur J. Sytkowski
From the Laboratory for Cell and Molecular Biology, Division of
Hematology and Oncology, Department of Medicine, Beth Israel Deaconess
Medical Center, Harvard Medical School, Boston, MA.
The hematopoietic growth factor erythropoietin (Epo) triggers
changes in the expression of genes that encode important regulators of
erythroid cell growth and differentiation. We now report that Epo
markedly upregulates chop (gadd153) expression and that
this transcription factor plays a role in erythropoiesis. Using a
differential hybridization assay, we isolated a full-length cDNA of
chop as an Epo upregulated gene in Rauscher murine
erythroleukemia cells. RNase protection assays demonstrated that Epo or
dimethyl sulfoxide induction increased steady-state mRNA levels 10- to
20-fold after 24 to 48 hours. Western blot analysis confirmed a marked
increase in CHOP protein. Among the other c/ebp family members,
only c/ebp  was also upregulated during erythroid
differentiation. Among normal hematopoietic cells examined,
steady-state mRNA levels were highest in erythroid cells, with levels
peaking during terminal differentiation. Transient overexpression of
chop in Rauscher cells resulted in a significant increase in
Epo- or dimethyl sulfoxide (DMSO)-induced hemoglobinization, further
linking chop upregulation to erythroid differentiation.
Artificial downregulation of chop in normal murine bone marrow
cells with antisense oligodeoxynucleotides inhibited colony-forming
unit-erythroid (CFU-E)-derived colony growth in a
concentration-dependent manner. Burst-forming unit-erythroid (BFU-E)-derived colony growth was not affected. Using a Far Western type of analysis, we detected several potential CHOP binding partners among the nuclear proteins of Rauscher cells. Importantly, the number
and relative abundance of these proteins changed with differentiation. The results strongly suggest that CHOP plays a role in erythropoiesis, possibly through interactions with both C/EBP and non-C/EBP family members.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. P. Pinto, S. Ribeiro, H. Pontes, S. Thowfeequ, D. Tosh, F. Carvalho, and G. Porto
Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBP{alpha}
Blood,
June 15, 2008;
111(12):
5727 - 5733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-J. Chen
Regulation of protein synthesis by the heme-regulated eIF2{alpha} kinase: relevance to anemias
Blood,
April 1, 2007;
109(7):
2693 - 2699.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kubota, D. H. Lee, M. Tsuchiya, C. S. Young, E. T. Everett, E. A. Martinez-Mier, M. L. Snead, L. Nguyen, F. Urano, and J. D. Bartlett
Fluoride Induces Endoplasmic Reticulum Stress in Ameloblasts Responsible for Dental Enamel Formation
J. Biol. Chem.,
June 17, 2005;
280(24):
23194 - 23202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gery, D. J. Park, P. T. Vuong, D. Y. Chih, N. Lemp, and H. P. Koeffler
Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes
Blood,
December 15, 2004;
104(13):
3911 - 3917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pomerance, D. Carapau, F. Chantoux, M. Mockey, C. Correze, J. Francon, and J.-P. Blondeau
CCAAT/Enhancer-Binding Protein-Homologous Protein Expression and Transcriptional Activity Are Regulated by 3',5'-Cyclic Adenosine Monophosphate in Thyroid Cells
Mol. Endocrinol.,
November 1, 2003;
17(11):
2283 - 2294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. MIKULITS, B. PRADET-BALADE, B. HABERMANN, H. BEUG, J. A. GARCIA-SANZ, and E. W. MÜLLNER
Isolation of translationally controlled mRNAs by differential screening
FASEB J,
August 1, 2000;
14(11):
1641 - 1652.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Cui, M. Coutts, J. Stahl, and A. J. Sytkowski
Novel Interaction between the Transcription Factor CHOP (GADD153) and the Ribosomal Protein FTE/S3a Modulates Erythropoiesis
J. Biol. Chem.,
March 10, 2000;
275(11):
7591 - 7596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. C. Mertani, T. Zhu, E. L. K. Goh, K.-O. Lee, G. Morel, and P. E. Lobie
Autocrine Human Growth Hormone (hGH) Regulation of Human Mammary Carcinoma Cell Gene Expression. IDENTIFICATION OF CHOP AS A MEDIATOR OF hGH-STIMULATED HUMAN MAMMARY CARCINOMA CELL SURVIVAL
J. Biol. Chem.,
June 8, 2001;
276(24):
21464 - 21475.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
