Prehn J, Mercola M, Calame K
Nucleic Acids Res. 1984 Dec 11;12(23):8987-9007. doi: 10.1093/nar/12.23.8987.
Plasmacytoma M603 contains one normal, nontranslocated c-myc gene and one translocated c-myc gene in which c-myc exon 1 is juxtaposed with the immunoglobulin heavy chain enhancer and c-myc exons 2 and 3 are juxtaposed with C alpha. We find that steady-state c-myc RNA levels are 2-4 fold elevated in M603 relative to normal liver or spleen and that these transcripts originate predominantly if not exclusively from the translocated c-myc gene. Although both promoters on the nontranslocated c-myc gene are repressed, the proximal promoter, P1, is active on the translocated 5' c-myc region which is juxtaposed with the immunoglobulin heavy chain enhancer. The 3' portion of the translocated c-myc gene is transcribed from fifteen cryptic start sites and spliced at aberrant donor and acceptor splice sites, thereby generating a mixture of transcripts with different, abnormal 5' untranslated regions. Although the reason that translocation activates the cryptic c-myc starts in M603 is not completely understood, we show that truncation of the c-myc gene is not sufficient to activate cryptic transcription sites.
浆细胞瘤M603含有一个正常的、未发生易位的c-myc基因和一个发生易位的c-myc基因，其中c-myc外显子1与免疫球蛋白重链增强子并列，c-myc外显子2和3与Cα并列。我们发现，相对于正常肝脏或脾脏，M603中稳态c-myc RNA水平升高了2至4倍，并且这些转录本主要（如果不是唯一）源自易位的c-myc基因。尽管未发生易位的c-myc基因上的两个启动子均被抑制，但近端启动子P1在与免疫球蛋白重链增强子并列的易位5' c-myc区域上是活跃的。易位的c-myc基因的3'部分从15个隐蔽起始位点转录，并在异常的供体和受体剪接位点进行剪接，从而产生具有不同异常5'非翻译区的转录本混合物。尽管尚不完全清楚易位激活M603中隐蔽的c-myc起始的原因，但我们表明c-myc基因的截短不足以激活隐蔽的转录位点。
