Nakanishi Y, Kihara K, Mizuno K, Masamune Y, Yoshitake Y, Nishikawa K
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5216-20. doi: 10.1073/pnas.89.12.5216.
Recent findings on the translocation of intact fibroblast growth factor (FGF) into the cell nucleus suggest that it functions directly in nuclear events. We examined the effect of human basic FGF (bFGF) on gene transcription in a cell-free system. When mouse genes encoding phosphoglycerate kinases 1 and 2 (Pgk-1 and Pgk-2) were transcribed by using nuclear extracts of Ehrlich ascites tumor cells, FGF affected transcription in different ways: in the presence of bFGF, transcription of the Pgk-1 gene was inhibited, whereas that of the Pgk-2 gene was enhanced. When viral genes were tested, transcription of the adenovirus major late DNA was slightly stimulated but that of the adenovirus early E1A DNA or the human immunodeficiency virus DNA was not changed by the addition of bFGF. Moreover, the presence of a distinct 5' upstream region of the Pgk-2 gene, which includes a negative cis-acting element, was required for transcription stimulation by bFGF. These results suggest that bFGF can regulate transcription directly in the nucleus in a gene-specific manner.
近期关于完整的成纤维细胞生长因子(FGF)易位至细胞核的研究结果表明,它在核内事件中直接发挥作用。我们在无细胞体系中检测了人碱性FGF(bFGF)对基因转录的影响。当使用艾氏腹水瘤细胞核提取物转录编码磷酸甘油酸激酶1和2(Pgk - 1和Pgk - 2)的小鼠基因时,FGF以不同方式影响转录:在bFGF存在的情况下,Pgk - 1基因的转录受到抑制,而Pgk - 2基因的转录则增强。当检测病毒基因时,添加bFGF后,腺病毒主要晚期DNA的转录受到轻微刺激,但腺病毒早期E1A DNA或人类免疫缺陷病毒DNA的转录未发生变化。此外,Pgk - 2基因独特的5'上游区域(包含一个负性顺式作用元件)的存在是bFGF刺激转录所必需的。这些结果表明,bFGF能够以基因特异性方式直接在细胞核中调节转录。