Pg. Lutz et al., Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells, P NAS US, 97(4), 2000, pp. 1601-1606
Citations number
45
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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) initial
ly was described as involved in proliferation of human leukemia cells. The
granulocyte colony-stimulating factor (G-CSF), which stimulates the prolife
ration of granulocytic precursors, up-regulates MBN expression. Here we sho
w 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 C-CSF responsive gene critical to factor-independent growth and indic
ate 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 sit
es is responsive to G-CSF treatment. Although PU.1. C/EBP, and c-Myb transc
ription factors all were critical for expression of MEN, its up-regulation
by G-CSF was associated mainly with PU.1. These findings suggest that MBN i
s an important target of PU.1 and a key protease for factor-independent gro
wth of hematopoietic cells.