D. Decesare et al., HETERODIMERIZATION OF C-JUN WITH ATF-2 AND C-FOS IS REQUIRED FOR POSITIVE AND NEGATIVE REGULATION OF THE HUMAN UROKINASE ENHANCER, Oncogene, 11(2), 1995, pp. 365-376
Dimerization plays a pivotal role in modulating the activity of the c-
Jun proto-oncogene product. Heterodimerization with activating transcr
iption factor-2 (ATF-2) alters the DNA-binding specificity of c-Jun, a
llowing its targeting to several cAMP responsive element (CRE)related
sequences, which control a subset of AP-1-responsive genes, Here me sh
ow that a c-Jun/ATF-2 heterodimer binds to the AP-1 site (nPA 5'-TRE)
essential for the activity of the human urokinase enhancer, conferring
on this element several distinctive regulatory properties. The c-Jun/
ATF-2 heterodimer was identified by binding competition assays, u.v. c
ross linking, and monospecific antibodies, In vitro binding studies re
vealed that the uPA 5'-TRE sequence is recognized by the cyclic AMP-un
responsive ATF-2 factor, but not by the cyclic AMP-inducible CREB, In
addition, in vivo studies suggest that ATF-2 can mediate, at the same
time, the activation of the c-Jun/ATF-2 site and the repression of the
canonical. collagenase AP-1 site. We report that heterodimerization w
ith c-Fos does not increase the binding of c-Jun to the uPA 5'-TRE, in
contrast to the increased binding at a consensus AP-1 site. Our data
further suggest that c-Fos can act as a repressor of the c-Jun/ATF-2 b
inding site, revealing an important functional difference, with respec
t to canonical AP-I elements.