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FGF2‐mediated upregulation of urokinase‐type plasminogen activator expression requires a MAP‐kinase dependent activation of poly(ADP‐ribose) polymerase
Author(s) -
Caldini Riccardo,
Barletta Emanuela,
Del Rosso Mario,
Giovannelli Lisa,
Chevanne Marta
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20096
Subject(s) - poly adp ribose polymerase , polymerase , microbiology and biotechnology , biology , biochemistry , chemistry , enzyme
Poly(ADP‐ribosyl)ation is a post‐translational modification of protein occurring in the nucleus by poly(ADP‐ribose) polymerase enzyme activity. The main role of poly(ADP‐ribose) polymerase system as “nick sensor” and DNA breaks repair is based on its activation via DNA strand breaks. Furthermore, poly(ADP‐ribose) polymerase modifies the binding to DNA of several transcriptional factors by poly(ADP‐ribosyl)ation, thereby regulating also transcriptional gene expression. We have analyzed whether poly(ADP‐ribose) polymerase activity is involved in basic fibroblast growth factor (FGF2)‐mediated upregulation of urokinase‐type plasminogen activator (uPA) mRNA. We demonstrated that specific inhibition of poly(ADP‐ribose) polymerase activity via 3‐aminobenzamide (3ABA) or NAD + deprivation prevents FGF2‐mediated uPA mRNA over‐expression and cell‐associated plasminogen activator (PA) production in GM7373 endothelial cell line. We verified that FGF2 stimulates poly(ADP‐ribose) polymerase activity by a DNA strand breaks‐independent manner which involves a mitogen‐activated protein kinases (MAPK)‐dependent pathway, as confirmed by using PD98059 inhibitor and anisomycin stimulation. Poly(ADP‐ribose) polymerase involved in this mechanism is mainly the 60 kDa molecular mass isoform, that presents an increase in serine phosphorylation in the presence of FGF2. © 2005 Wiley‐Liss, Inc.