CLONING AND CHARACTERIZATION OF THE HUMAN PIM-1 GENE - A PUTATIVE ONCOGENE RELATED TO THE PROTEIN-KINASES

CLONING AND CHARACTERIZATION OF THE HUMAN PIM-1 GENE - A PUTATIVE ONCOGENE RELATED TO THE PROTEIN-KINASES
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DOI:
10.1002/jcb.240350204
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发表时间:
1987-10-01
影响因子:
4
通讯作者:
CROCE, CM
CROCE, CM
中科院分区:
生物学2区
文献类型:
--
作者:
MEEKER, TC;NAGARAJAN, L;CROCE, CM

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小鼠PIM-1基因与逆转录病毒相关的小鼠淋巴瘤的进化有关。我们已经开始了人类PIM-1基因的研究,因为它作为一个人类癌基因的潜在重要性。我们已经分离出该基因的基因组和cDNA克隆,并详细描述了该位点。预测的PIM-1蛋白长度为313个氨基酸。它与许多蛋白激酶具有同源性,但不具有跨膜区。对应于pp 60 v-src的tryosine-416的氨基酸是酪氨酸(位置198),这与PIM-1是酪氨酸激酶而不是丝氨酸-苏氨酸激酶的假设一致。发现PIM-1基因具有来自5 kb基因组DNA的6个外显子和5个内含子。S1核酸酶保护研究表明,成熟的PIM-1 mRNA的长度约为2.7 kb的转录起始位点的本地化。该基因的启动子没有TATA或CAAT盒,但有多个GC盒(CCGCCC),可能结合Sp1蛋白。PIM-1基因在髓系和B淋巴细胞系中表达,而在T淋巴细胞系和非造血细胞系中不表达。PIM-1的这种初步表征将使我们能够确定其在正常和恶性血液淋巴细胞分化中的作用。
The mouse PIM-1 gene has been implicated in the evolution of retrovirus-associated mouse lymphomas. We have initiated a study of the human PIM-1 gene because of its potential importance as a human oncogene. We have isolated genomic and cDNA clones for this gene and characterized this locus in detail. The predicted PIM-1 protein is 313 amino acids in length. It has homology to a number of the protein kinases but does not have a transmembrane region. The amino acid corresponding to tryosine-416 of pp60v-src is a tyrosine (position 198), which is consistent with the hypothesis that PIM-1 is a tyrosine kinase rather than a serine-threonine kinase. The PIM-1 gene was found to have six exons and five introns derived from 5 kb of genomic DNA. The site of transcription initiation was localized by S1 nuclease protection studies which indicated that the mature PIM-1 mRNA was approximately 2.7 kb in length. The promotor of this gene had no TATA or CAAT box but did have multiple GC boxes (CCGCCC) that might bind the Sp1 protein. The PIM-1 gene was expressed in myeloid and B lymphoid cell lines, but not in T lymphoid and nonhemopoietic lines. This initial characterization of PIM-1 will allow us to define its role in normal and malignant hematolymphoid differentiation.