Ypt. Au et al., HEPARIN DECREASES ACTIVATOR PROTEIN-1 BINDING TO DNA IN PART BY POSTTRANSLATIONAL MODIFICATION OF JUN-B, Circulation research, 75(1), 1994, pp. 15-22
Heparin is a potent inhibitor of the proliferation and migration of va
scular smooth muscle cells. This agent selectively inhibits the transc
ription of tissue-type plasminogen activator and interstitial collagen
ase, probably by decreasing the binding of activator protein-1 (AP-1)
to phorbol ester-responsive elements in the promoters of these genes.
Decreased AP-1 binding is not due to a direct inhibition by heparin, s
ince heparinase digestion of nuclear extracts prepared from heparin-tr
eated smooth muscle cells does not restore AP-1 binding activity. Trea
tment of cells with heparin suppresses the expression of Jun B, one of
the components of AP-1. The major effect of heparin is at the level o
f posttranslational modification of Jun B. Results from pulse-chase la
beling experiments show that the newly synthesized Jun B is rapidly co
nverted to a higher-molecular-weight form and that conversion is suppr
essed by heparin. Evidence is presented suggesting that the heparin-in
hibited event is phosphorylation of Jun B.