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J Biol Chem, Vol. 273, Issue 47, 31119-31124, November 20, 1998
§,§,§
From the Endothelial cell differentiation is a crucial
step in angiogenesis. Here we report the identification of EDF-1, a
novel gene product that is down-regulated when endothelial cells are
induced to differentiate in vitro. The cDNA encoding
EDF-1 was isolated by RNA fingerprinting from human
endothelial cells exposed to human immunodeficiency virus type 1 Tat, a
viral protein known to be angiogenic. The deduced amino acid sequence
of EDF-1 encodes a basic intracellular protein of 148 amino acids that
is homologous to MBF1 (multiprotein-bridging
factor 1) of the silkworm Bombyx mori and to H7, which is implicated in the early developmental events of Dictyostelium discoideum. Interestingly, human
immunodeficiency virus type 1 Tat, which affects endothelial functions,
and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
and culture on fibrin gels, which promote endothelial differentiation
in vitro, all down-regulate EDF-1 expression
both at the RNA and protein levels. In addition, the inhibition of
EDF-1 translation by an antisense anti-EDF-1 construct results in the
inhibition of endothelial cell growth and in the transition from a
nonpolar cobblestone phenotype to a polar fibroblast-like phenotype.
These data suggest that EDF-1 may play a role in the regulation of
human endothelial cell differentiation.
Dipartimento di Scienze e Tecnologie
Biomediche-Ospedale San Raffaele,
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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