Raschellà G, Tanno B, Bonetto F, Negroni A, Claudio P P, Baldi A, Amendola R, Calabretta B, Giordano A, Paggi M G
Section of Toxicology and Biomedical Sciences, Ente Nuove Tecnologie Energia e Ambiente (ENEA) Via Anguillarese 301, 00060 Rome, Italy.
Cell Death Differ. 1998 May;5(5):401-7. doi: 10.1038/sj.cdd.4400359.
The retinoblastoma family of nuclear factors is composed of RB, the prototype of the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130. The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and are involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RB family gene products during the DMSO-induced differentiation of the N1E-115 murine neuroblastoma cells. In this system, pRb2/p130 was strongly up-regulated during mid-late differentiation stages, while, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RB family genes in these cells was able, at different degrees, to induce neuronal differentiation, to inhibit [3H]thymidine incorporation and to down-regulate the activity of the B-myb promoter.
核因子视网膜母细胞瘤家族由RB(肿瘤抑制基因的原型)以及与之密切相关的基因p107和Rb2/p130组成。这三个基因编码的蛋白质,即pRb、p107和pRb2/p130,具有相似的结构和功能。这些蛋白质在许多细胞类型中经常同时表达,并参与细胞增殖和分化的调控。我们测定了在二甲基亚砜(DMSO)诱导的N1E-115小鼠神经母细胞瘤细胞分化过程中RB家族基因产物的表达和磷酸化情况。在这个系统中,pRb2/p130在分化中后期强烈上调,而相反,pRb和p107在后期显著下降。正在分化的N1E-115细胞还显示出B-myb水平的逐渐降低,B-myb是一种与增殖相关的蛋白质,其组成性表达会抑制神经元分化。将RB家族的每个基因转染到这些细胞中,在不同程度上能够诱导神经元分化、抑制[3H]胸腺嘧啶核苷掺入并下调B-myb启动子的活性。