TRANS-REPRESSOR ACTIVITY OF NUCLEAR GLYCOSAMINOGLYCANS ON FOS AND JUN/AP-1 ONCOPROTEIN-MEDIATED TRANSCRIPTION
TRANS-REPRESSOR ACTIVITY OF NUCLEAR GLYCOSAMINOGLYCANS ON FOS AND JUN/AP-1 ONCOPROTEIN-MEDIATED TRANSCRIPTION
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DOI：
10.1083/jcb.116.1.31
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发表时间：
1992-01-01
影响因子：
7.8
通讯作者：
JACKSON, RL
中科院分区：
文献类型：
--
作者：
BUSCH, SJ;MARTIN, GA;JACKSON, RL
肝素阻断佛波酯诱导的非转化细胞通过G 0/G1期的进程（Wright，T.C.，L. A. Pukac，J. J. Castellot，M.卡尔诺夫斯基河A. Levine，H. Y. Kim-Park和J. Campisi。1989. Proc. Natl. Acad. Sci. USA. 86：3199-3203）或Gl至S期（Reilly，C. F.、M. S. Kindy，K. E.布朗河D. Rosenberg和G. E.索南辛1989. J.Biol.Chem.264：6990-6995）。细胞周期停滞与阶段特异性mRNA水平降低相关，表明细胞生长的转录调控。在本报告中，我们表明，肝素选择性抑制TPA诱导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畸胎瘤细胞中观察到肝素诱导的反式阻遏。肝素和戊聚糖多硫酸酯对AP-1介导的反式激活有抑制作用，但硫酸软骨素A或C则无此作用。肝素结合肽或肝素酶I除了肝素处理的细胞的核裂解物允许增强内源性AP-1特异性DNA结合活性的恢复。我们提出了一个模型，其中核糖胺聚糖发挥反式调节作用，改变诱导基因表达的模式。
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.