Lai F, Godley L A, Fernald A A, Orelli B J, Pamintuan L, Zhao N, Le Beau M M
Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, USA.
Genomics. 2000 Nov 15;70(1):123-30. doi: 10.1006/geno.2000.6345.
Loss of a whole chromosome 5, or a del(5q), is a recurring abnormality in malignant myeloid diseases. By cytogenetic and molecular analyses, we delineated previously a 1- to 1.5-Mb region that is deleted in all patients with a del(5q). In our efforts to identify a myeloid tumor suppressor gene within the commonly deleted segment (CDS), we have cloned and characterized the genes encoding three putative nuclear proteins, each of which contains a bipartite nuclear localization signal (NLS). In addition, C5ORF5 contains a putative rhoGAP domain at the N-terminus, C5ORF6 has a proline-rich sequence near the N-terminus, and C5ORF7 has a zinc-finger domain that partially overlaps the NLS. All three genes are ubiquitously expressed and encode novel proteins. The C5ORF5 cDNA is 5.47 kb encoding a protein of 915 amino acids (aa) with a predicted molecular mass of approximately 105 kDa. C5ORF5 has 23 exons spanning over 27 kb. The C5ORF6 transcript is 4.1 kb encoding a protein of 392 aa with a predicted molecular mass of approximately 43 kDa. C5ORF6 has 5 exons and spans approximately 11 kb. The C5ORF7 cDNA is 6.3 kb and encodes a protein of 1417 aa with a predicted molecular mass of approximately 155 kDa. C5ORF7 has 24 exons spanning approximately 64 kb. All three genes were localized to the distal half of the CDS between D5S1983 and D5S500. We evaluated each as a candidate tumor suppressor gene by the analysis of myeloid leukemia cells from patients with -5/del(5q), but no inactivating mutations were identified.
整条5号染色体缺失，即del(5q)，是恶性髓系疾病中反复出现的异常情况。通过细胞遗传学和分子分析，我们之前划定了一个1至1.5兆碱基的区域，所有del(5q)患者的该区域均有缺失。在我们识别常见缺失片段（CDS）内髓系肿瘤抑制基因的过程中，我们克隆并鉴定了编码三种假定核蛋白的基因，每个基因都包含一个双分核定位信号（NLS）。此外，C5ORF5在N端含有一个假定的rhoGAP结构域，C5ORF6在N端附近有一个富含脯氨酸的序列，C5ORF7有一个与NLS部分重叠的锌指结构域。这三个基因均广泛表达并编码新蛋白。C5ORF5 cDNA为5.47 kb，编码一个含915个氨基酸（aa）的蛋白，预测分子量约为105 kDa。C5ORF5有23个外显子，跨越超过27 kb。C5ORF6转录本为4.1 kb，编码一个含392个aa的蛋白，预测分子量约为43 kDa。C5ORF6有5个外显子，跨度约为11 kb。C5ORF7 cDNA为6.3 kb，编码一个含1417个aa的蛋白，预测分子量约为155 kDa。C5ORF7有24个外显子，跨度约为64 kb。这三个基因均定位于CDS的远端，在D5S1983和D5S500之间。我们通过分析-5/del(5q)患者的髓系白血病细胞，将每个基因评估为候选肿瘤抑制基因，但未发现失活突变。
