Jackers P, Minoletti F, Belotti D, Clausse N, Sozzi G, Sobel M E, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
Oncogene. 1996 Aug 1;13(3):495-503.
The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional protein involved in the translational machinery and has also been identified as p40 ribosome-associated protein. Although highly conserved cDNAs corresponding to this polypeptide have been isolated from several species including vertebrates, invertebrates, plants and prokaryotes, characterization of any of the corresponding active genes has never been reported. In this study, we have cloned an intron-containing fragment which permitted us to isolate the active 37LRP/p40 human gene. This gene contains seven exons and six introns. Ribonuclease protection experiments suggest multiple transcription start sites. The promoter area does not bear a TATA box but contains four Sp1 sites. The first intron is also GC rich containing five Sp1 sites. Intron 4 contains the full sequence of the small nuclear RNA E2 and two Alu sequences are found in intron 3. Fluorescent in situ hybridization localized the 37LRP/p40 active gene on chromosome 3 in the locus 3p21.3 which, interestingly, is a hot spot for genetic alterations in several cancers and particularly in small cell lung carcinoma.
67kD层粘连蛋白受体（37LRP）的37kD前体是一种多肽，其表达在侵袭性癌中持续上调。有趣的是，37LRP似乎是一种参与翻译机制的多功能蛋白，也被鉴定为p40核糖体相关蛋白。尽管已经从包括脊椎动物、无脊椎动物、植物和原核生物在内的几个物种中分离出了与该多肽对应的高度保守的cDNA，但尚未有任何相应活性基因的表征报道。在本研究中，我们克隆了一个含内含子的片段，该片段使我们能够分离出活性37LRP/p40人类基因。该基因包含七个外显子和六个内含子。核糖核酸酶保护实验表明有多个转录起始位点。启动子区域没有TATA框，但包含四个Sp1位点。第一个内含子也富含GC，包含五个Sp1位点。内含子4包含小核RNA E2的完整序列，内含子3中发现两个Alu序列。荧光原位杂交将37LRP/p40活性基因定位在3号染色体上的3p21.3位点，有趣的是，该位点是几种癌症特别是小细胞肺癌中基因改变的热点。
