CONSTRUCTION OF A 2.8-MEGABASE YEAST ARTIFICIAL CHROMOSOME CONTIG AND CLONING OF THE HUMAN METHYLTHIOADENOSINE PHOSPHORYLASE GENE FROM THE TUMOR-SUPPRESSOR REGION ON 9P21
CONSTRUCTION OF A 2.8-MEGABASE YEAST ARTIFICIAL CHROMOSOME CONTIG AND CLONING OF THE HUMAN METHYLTHIOADENOSINE PHOSPHORYLASE GENE FROM THE TUMOR-SUPPRESSOR REGION ON 9P21
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DOI：
10.1073/pnas.92.14.6489
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发表时间：
1995-07-03
影响因子：
11.1
通讯作者：
BOHLANDER, SK
中科院分区：
文献类型：
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作者：
OLOPADE, OI;POMYKALA, HM;BOHLANDER, SK
许多人类恶性肿瘤细胞缺乏甲硫腺苷磷酸化酶（MTAP）酶活性，编码这种酶的基因（MTAP）先前定位于9号染色体的短臂，p21-22带，这是一个在多种肿瘤类型中经常缺失的区域。为了从9 p21 -22的缺失区域克隆候选抑癌基因，我们利用重叠酵母人工染色体和粘粒克隆构建了9 p21的2.8兆碱基的长距离物理图谱。该图谱包括I型IFN基因簇、最近发现的候选肿瘤抑制基因CDKN 2（p16（INK 4A））和CDKN 2B（p15（INK 4 B））以及几个CpG岛，此外，我们还发现了酵母人工染色体重叠群中的其他转录单位。对从定位在IFN基因和CDKN 2之间的CpG岛分离的2，5-kb cDNA克隆的序列分析揭示了预测的283个氨基酸的开放阅读框架，随后是1302个核苷酸的3'非翻译序列。该基因在进化上是保守的，并显示出与小鼠和人嘌呤核苷磷酸化酶以及与红杜鹃pet基因（编码细胞色素bc（1）复合物）区域中的假定25.8 kDa蛋白质的显著氨基酸同源性。该基因的位置、表达模式和核苷酸序列表明它编码MTAP酶。
Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity, The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type I IFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16(INK4A)) and CDKN2B (p15(INK4B)), and several CpG islands, In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2,5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3' untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8 kDa protein in the pet gene (coding for cytochrome bc(1) complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequence of this gene suggest that it codes for the MTAP enzyme.