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Inhibition of erythro-myeloid differentiation by constitutive expression of
a DNA binding-deficient c-myb mutant: implication for c- myb function
A Sala, T Bellon, P Melotti, C Peschle and B Calabretta
Department of Microbiology and Immunology, Jefferson Cancer Institute,
Thomas Jefferson University, Philadelphia, PA 19107, USA.
The c-myb proto-oncogene encodes a nuclear protein involved in the
regulation of cell proliferation, differentiation, and development. Myb
protein contains a DNA binding and a transactivating domain thought to
mediate its biologic properties. The DNA binding domain consists of three
repeats (R1, R2, and R3), each containing a highly conserved motif of
tryptophan residues. A c-myb mutant (DR1-myb) lacking the last 46 amino
acids of R1 and 23 amino terminal residues of R2, a region homologous to
the ADA-2 yeast transcriptional adaptor, lost DNA binding ability, but
remained able to transactivate the human heat-shock promoter. Transfection
of murine 32D and murine erythroleukemia (MEL) cell lines with DR1-myb
caused inhibition of cellular differentiation induced by granulocyte
colony-stimulating factor (G-CSF) and dimethyl sulfoxide (DMSO),
respectively. A second c-myb mutant (D-ADA2-myb) lacking the first 23 amino
acids of R2, also lost DNA binding and transactivation activity, but did
not inhibit DMSO-induced differentiation of MEL transfected cells. These
findings suggest that deletion of R1 activates a DNA binding-independent
mechanism of c-myb function, which may involve interaction of Myb with
cellular factors.
Volume 86,
Issue 9,
pp. 3404-3412,
11/01/1995
Copyright © 1995 by The American Society of Hematology

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