EDF-1, a novel gene product down-regulated in human endothelial cell differentiation.
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.
Dragoni
I
I
Dipartimento di Scienze e Tecnologie Biomediche-Ospedale San Raffaele, Università di Milano, I-20132 Milano, Italy.
Mariotti
M
M
Consalez
G G
GG
Soria
M R
MR
Maier
J A
JA
D000595:Amino Acid Sequence; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins; D002454:Cell Differentiation; D003001:Cloning, Molecular; D017124:Conserved Sequence; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D019143:Evolution, Molecular; D015696:Gene Products, tat / Q000494:pharmacology; D015497:HIV-1; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D054322:tat Gene Products, Human Immunodeficiency Virus
D002148:Calmodulin-Binding Proteins; C115911:EDF1 protein, human; D015696:Gene Products, tat; D011506:Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus