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The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation.
- Source :
-
Blood [Blood] 2003 Jul 15; Vol. 102 (2), pp. 712-7. Date of Electronic Publication: 2003 Mar 27. - Publication Year :
- 2003
-
Abstract
- Transcriptional profiles of cultured primary human erythroid cells were examined to identify those genes involved in the control of erythroid growth during the terminal phase of maturation. Our in silico screening strategy indicated that a hypoxia-inducible proapoptotic member of the Bcl-2 gene family called Nix is expressed during erythropoiesis. We next performed Northern blot analyses and determined that the 1.4-kb Nix transcript is expressed at lower levels in erythroleukemia cells than reticulocytes. Polymerase chain reaction (PCR)-based transcriptional patterning confirmed the increased expression of Nix during human erythropoiesis with a pattern similar to that of Bcl-xL and glycophorin A and opposite that of Bcl-2. Western blot analyses revealed Nix protein levels that were lower than expected due to increased proteosomal degradation. The expression of Nix and Bcl-xL proteins decreased relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) control on the removal of erythropoietin (EPO) from the culture medium. Immunocytochemical analyses demonstrated a similar perinuclear mitochondrial expression pattern for both proteins in hemoglobinized precursors. On the basis of these data, we propose that the proapoptotic factor Nix is a highly regulated effector of growth during terminal erythroid maturation.
- Subjects :
- Apoptosis genetics
Blotting, Western
Cell Differentiation drug effects
Cell Differentiation genetics
Cysteine Endopeptidases metabolism
Erythroid Precursor Cells cytology
Erythroid Precursor Cells drug effects
Erythropoietin pharmacology
Gene Expression Regulation drug effects
Glycophorins biosynthesis
Glycophorins genetics
Humans
Leukemia, Erythroblastic, Acute genetics
Leukemia, Erythroblastic, Acute metabolism
Leukemia, Erythroblastic, Acute pathology
Membrane Proteins genetics
Membrane Proteins physiology
Multienzyme Complexes metabolism
Polymerase Chain Reaction
Proteasome Endopeptidase Complex
Proto-Oncogene Proteins c-bcl-2 genetics
RNA, Messenger biosynthesis
RNA, Messenger genetics
Reticulocytes drug effects
Reticulocytes metabolism
Transcription, Genetic drug effects
Tumor Cells, Cultured metabolism
bcl-X Protein
Erythroid Precursor Cells metabolism
Erythropoiesis genetics
Membrane Proteins biosynthesis
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Tumor Suppressor Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 102
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 12663450
- Full Text :
- https://doi.org/10.1182/blood-2002-11-3324