Palmero I, Holder A, Sinclair A J, Dickson C, Peters G
Imperial Cancer Research Fund Laboratories, London, UK.
Oncogene. 1993 Apr;8(4):1049-54.
The cyclin D1 gene can be transcriptionally activated in lymphoid tumours as a result of chromosomal rearrangements but is normally silent in B and T lymphocytes. By isolating cyclin D1-related cDNAs from a B-lymphoid cell line, we identified clones that contain the coding sequences of human cyclin D2. The predicted 289 amino acid protein shares 63% identity with human cyclin D1. Although cyclin D2 transcripts were detected in many lymphoid cell lines, it was not ubiquitously expressed and there was no apparent correlation with cyclin D1 levels. For example, two B-cell leukaemia lines, JVM-2 and Karpas 620, both of which have 11q13 translocations and express cyclin D1, contained markedly different amounts of cyclin D2. An obvious distinction between these cells is that the JVM-2 line, which expresses high levels of cyclin D2, was immortalized by Epstein-Barr virus (EBV). We subsequently found that cyclin D2 is consistently expressed in group III Burkitt's lymphoma (BL) and in lymphoblastoid cell lines immortalized by EBV, but not in group I BLs, in which expression of the EBV genome is more restricted. The data imply that the D-type cyclins may have non-overlapping functions at specific stages of lymphocyte differentiation and that the expression of cyclin D2 may be influenced, directly or indirectly, by EBV.
细胞周期蛋白D1基因可因染色体重排而在淋巴瘤中被转录激活,但在B和T淋巴细胞中通常是沉默的。通过从一个B淋巴细胞系中分离细胞周期蛋白D1相关的cDNA,我们鉴定出了包含人细胞周期蛋白D2编码序列的克隆。预测的289个氨基酸的蛋白质与人细胞周期蛋白D1有63%的同源性。虽然在许多淋巴细胞系中检测到了细胞周期蛋白D2转录本,但它并非普遍表达,且与细胞周期蛋白D1水平没有明显的相关性。例如,两个B细胞白血病系JVM-2和Karpas 620,它们都有11q13易位并表达细胞周期蛋白D1,但所含细胞周期蛋白D2的量明显不同。这些细胞之间的一个明显区别是,表达高水平细胞周期蛋白D2的JVM-2系是由爱泼斯坦-巴尔病毒(EBV)永生化的。我们随后发现,细胞周期蛋白D2在III组伯基特淋巴瘤(BL)和由EBV永生化的淋巴母细胞系中持续表达,但在I组BL中不表达,在I组BL中EBV基因组的表达受到更多限制。数据表明,D型细胞周期蛋白可能在淋巴细胞分化的特定阶段具有非重叠功能,且细胞周期蛋白D2的表达可能直接或间接受EBV影响。