Busch S J, Martin G A, Barnhart R L, Mano M, Cardin A D, Jackson R L
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
J Cell Biol. 1992 Jan;116(1):31-42. doi: 10.1083/jcb.116.1.31.
Heparin blocks the phorbol ester-induced progression of nontransformed cells through the G0/G1 phase (Wright, T.C., L.A. Pukac, J.J. Castellot, M.J. Karnovsky, R.A. Levine, H.-Y. Kim-Park, and J. Campisi. 1989. Proc. Natl. Acad. Sci. USA. 86: 3199-3203) or G1 to S phase (Reilly, C. F., M. S. Kindy, K. E. Brown, R. D. Rosenberg, and G. E Sonenshein. 1989. J. Biol. Chem. 264:6990-6995) of the cell cycle. Cell cycle arrest was associated with decreased levels of stage-specific mRNAs suggesting transcriptional regulation of cell growth. In the present report, we show that heparin selectively repressed TPA-inducible AP-1-mediated gene expression. Heparin-induced trans-repression was observed in primary vascular smooth muscle cells, as well as in the transformed HeLa cell line and in nondifferentiated F9 teratocarcinoma cells. Inhibition of AP-1-mediated trans-activation occurred with heparin and pentosan polysulfate but not with chondroitin sulfate A or C. Heparin-binding peptides or heparitinase I addition to nuclear lysates of heparin-treated cells allowed enhanced recovery of endogenous AP-1-specific DNA binding activity. We propose a model in which nuclear glycosaminoglycans play a trans-regulatory role in altering the patterns of inducible gene expression.
肝素可阻断佛波酯诱导的未转化细胞通过细胞周期的G0/G1期（赖特，T.C.，L.A. 普卡克，J.J. 卡斯特洛特，M.J. 卡尔诺夫斯基，R.A. 莱文，H.-Y. 金-帕克，以及J. 坎皮西。1989年。美国国家科学院院刊。86: 3199 - 3203）或从G1期到S期（赖利，C.F.，M.S. 金迪，K.E. 布朗，R.D. 罗森伯格，以及G.E. 索南申。1989年。生物化学杂志。264:6990 - 6995）。细胞周期停滞与阶段特异性mRNA水平降低相关，提示细胞生长受转录调控。在本报告中，我们表明肝素选择性抑制佛波酯诱导的AP - 1介导的基因表达。在原代血管平滑肌细胞、转化的HeLa细胞系和未分化的F9畸胎癌细胞中均观察到肝素诱导的反式抑制。肝素和戊聚糖多硫酸盐可抑制AP - 1介导的反式激活，而硫酸软骨素A或C则无此作用。向肝素处理细胞的核裂解物中添加肝素结合肽或肝素酶I可增强内源性AP - 1特异性DNA结合活性的恢复。我们提出一个模型，其中核糖胺聚糖在改变诱导基因表达模式中发挥反式调节作用。
