Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells.

Abstract

Hematopoiesis depends on a pool of quiescent hematopoietic stem/progenitor cells. When exposed to specific cytokines, a portion of these cells enters the cell cycle to generate an amplified progeny. Myeloblastin (MBN) initially was described as involved in proliferation of human leukemia cells. The granulocyte colony-stimulating factor (G-CSF), which stimulates the proliferation of granulocytic precursors, up-regulates MBN expression. Here we show that constitutive overexpression of MBN confers factor-independent growth to murine bone marrow-derived Ba/F3/G-CSFR cells. Our results point to MBN as a G-CSF responsive gene critical to factor-independent growth and indicate that expression of the G-CSF receptor is a prerequisite to this process. A 91-bp MBN promoter region containing PU.1, C/EBP, and c-Myb binding sites is responsive to G-CSF treatment. Although PU.1, C/EBP, and c-Myb transcription factors all were critical for expression of MBN, its up-regulation by G-CSF was associated mainly with PU.1. These findings suggest that MBN is an important target of PU.1 and a key protease for factor-independent growth of hematopoietic cells.

• Authors: P G Lutz, C Moog-Lutz, E Coumau-Gatbois, L Kobari, Y Di Gioia, Y E Cayre
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 4 Pg. 1601-6 (Feb 15 2000) ISSN: 0027-8424 [Print] United States
• PMID: 10677505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins
• Nuclear Proteins
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-myb
• Receptors, Granulocyte Colony-Stimulating Factor
• Trans-Activators
• Transcription Factors
• proto-oncogene protein Spi-1
• Granulocyte Colony-Stimulating Factor
• Serine Endopeptidases
• Myeloblastin

Topics

• Animals
• Antigens, CD34 (immunology)
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins (metabolism)
• Gene Expression Regulation
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Hematopoietic Stem Cells (drug effects)
• Humans
• Mice
• Myeloblastin
• Nuclear Proteins (metabolism)
• Promoter Regions, Genetic
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-myb (metabolism)
• Receptors, Granulocyte Colony-Stimulating Factor (metabolism)
• Serine Endopeptidases (genetics, metabolism)
• Trans-Activators (metabolism)
• Transcription Factors (metabolism)
• Transfection
• Tumor Cells, Cultured