The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia
The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia
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DOI：
10.1006/excr.1998.4201
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发表时间：
1998-11-01
影响因子：
3.7
通讯作者：
Bell, JC
中科院分区：
文献类型：
--
作者：
Abraham, N;Jaramillo, ML;Bell, JC
双链RNA依赖性激酶PKR由干扰素诱导基因编码，主要负责该细胞因子的抗病毒作用。最近的研究表明，PKR也可能在正常细胞生长的调节中发挥作用。尽管存在许多PKR失活的病毒策略的例子，但没有证据表明PKR在肿瘤中失活。我们在这里证明，Tik基因，它编码的双特异性激酶，是鼠同源PKR，dsRNA依赖性激酶，并已经历了一个等位基因在小鼠淋巴细胞白血病细胞的重排。我们已经克隆了一个cDNA，对应于从重排的mPKR基因的突变的转录本，并显示，而突变的多肽保留其二聚化和结合dsRNA的能力，它是催化失活。虽然这种突变的mPKR缺乏明显的显性负功能，但这些细胞中PKR活性降低的净效应可能是显著的。(C)北京：科学出版社.
The double-stranded RNA-dependent kinase, PKR, is encoded by an interferon inducible gene and is largely responsible for the anti-viral effects of this cytokine. Recent studies have shown that PKR may also play a role in the regulation of normal cellular growth. Although numerous examples of viral strategies for inactivation of PKR exist, there is no evidence of PKR inactivation in tumors. We demonstrate here that the Tik gene, which encodes a dual-specificity kinase, is the murine homolog of PKR, the dsRNA-dependent kinase, and has undergone a rearrangement of one allele in a murine lymphocytic leukemia cell. We have cloned a cDNA that corresponds to a mutated transcript from the rearranged mPKR gene and show that while the mutated polypeptide retains its ability to dimerize and bind dsRNA, it is catalytically inactive. Although this mutated mPKR lacks apparent dominant-negative function, the net effect of reduced PKR activity in these cells may be significant. (C) 1998 Academic Press.