NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth
NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth
复制标题
DOI：
10.1128/mcb.21.15.4996-5007.2001
复制
发表时间：
2001-08-01
影响因子：
5.3
通讯作者：
Kiefer, P
中科院分区：
文献类型：
--
作者：
Reimers, K;Antoine, M;Kiefer, P
分泌型和核型成纤维细胞生长因子3(FGF3)对细胞有相反的作用。分泌型促进细胞生长和转化，而核型抑制DNA合成和细胞增殖。利用酵母双杂交系统，我们在COS-1细胞中鉴定了核仁FGF3结合蛋白(NOBP)，该蛋白与FGF3免疫共沉淀和共定位。对FGF3的NOBP结合域的鉴定完全符合FGF3转位到核仁中的序列要求，这表明NOBP可能是FGF3的核仁结合伙伴，对其核仁定位是必不可少的。NOBP的羧基末端结构域含有线性的核和核仁靶向基序，这些基序能够将异源蛋白B-半乳糖苷酶定向到核和核仁。在所有已建立的增殖分析细胞系中均检测到NOBP的表达，而在诱导分化时，早幼粒白血病细胞系HL60中的NOBP转录迅速下调。对洛伐他汀诱导的HeLa细胞周期中NOBP mRNA表达模式的分析表明，在G(1)晚期/S早期，NOBP mRNA的表达显著上调。NOBP过表达对NIH3T3细胞有促增殖作用，并能拮抗核FGF3的抑制作用，提示NOBP在细胞增殖中具有调控作用。我们认为NOBP是核FGF3作用的功能靶点。
Secreted and nuclear forms of fibroblast growth factor 3 (FGF3) have opposing effects on cells. The secreted form stimulates cell growth and transformation, while the nuclear form inhibits DNA synthesis and cell proliferation. By using the yeast two-hybrid system we have identified a nucleolar FGF3 binding protein (NoBP) which coimmunoprecipitated and colocalized with FGF3 in transfected COS-1 cells. Characterization of the NoBP binding domain of FGF3 exactly matched the sequence requirements of FGF3 for its translocation into the nucleoli, suggesting that NoBP might be the nucleolar binding partner of FGF3 essential for its nucleolus localization. Carboxyl-terminal domains of NoBP contain linear nuclear and nucleolar targeting motifs which are capable of directing a heterologous protein B-galactosidase to the nucleus and the nucleoli. While NoBP expression was detected in all analyzed proliferating established cell lines, NoBP transcription was rapidly downreguIated in the promyelocytic leukemia cell line HL60 when induced to differentiate. Analysis on the expression pattern of NoBP mRNA throughout the cell cycle in HeLa cells synchronized by lovastatin demonstrated a substantial upregulation during the late G(1)/early S phase. NoBP overexpression conferred a proliferating effect onto NIH 3T3 cells and can counteract the inhibitory effect of nuclear FGF3, suggesting a role of NoBP in controlling proliferation in cells. We propose that NoBP is the functional target of nuclear FGF3 action.