Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA.
Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA.
复制标题
克隆一种新型恶性黑色素瘤衍生生长调节蛋白 MIA。
作者：
A. Blesch;A. Bosserhoff;R. Apfel;Christian Behl;B. Hessdoerfer;A. Schmitt;P. Jachimczak;F. Lottspeich;R. Buettner;U. Bogdahn
恶性黑色素瘤细胞的生长和发展受到肿瘤细胞和局部环境产生的生长刺激和抑制因子的复杂网络的影响。在这里，我们报道了一种新的生长调节蛋白的纯化和分子克隆，命名为黑色素瘤抑制活性(MIA)，并提供了初步的功能鉴定。MIA被翻译为一个131个氨基酸的前体，在切割一个假定的分泌信号后被加工成一个成熟的107个氨基酸的蛋白质。分离到一种小鼠互补DNA，编码一种氨基酸同源性为88%的MIA蛋白。MIA由几种恶性黑色素瘤细胞株分泌到培养上清液中，作为M(R)11000自分泌生长因子，对恶性黑色素瘤细胞和其他神经外胚层肿瘤(包括胶质瘤)具有强大的肿瘤细胞生长抑制作用。MIA与任何其他已知的蛋白质没有同源性，因此代表了一种新型的生长调节因子。此外，我们描述了一种在大肠杆菌中表达具有功能活性的MIA的分子方法，这可能是一种很有吸引力的未来抗肿瘤治疗物质。
Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization. MIA is translated as a 131-amino acid precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal. A murine complementary DNA was isolated that encoded a MIA-protein with 88% amino acid identity. MIA is secreted into the culture supernatant by several malignant melanoma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas. MIA has no homology to any other known protein and, therefore, represents a novel type of growth-regulatory factor. Furthermore, we describe a molecular approach to express functionally active MIA in Escherichia coli, which might be attractive as a future antitumor therapeutical substance.