Comparative expression of tristetraprolin (TTP) family member transcripts in normal human tissues and cancer cell lines
Comparative expression of tristetraprolin (TTP) family member transcripts in normal human tissues and cancer cell lines
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DOI：
10.1016/j.abb.2007.04.011
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发表时间：
2007-06-15
影响因子：
3.9
通讯作者：
Blackshear, Perry J.
中科院分区：
文献类型：
--
作者：
Carrick, Danielle M.;Blackshear, Perry J.
Tristetraprolin(TTP)家族是串联锌指蛋白家族，在人类和大多数其他哺乳动物中由三个成员组成，第四个成员在啮齿动物中表达。在小鼠中，TTP基因的破坏本身会导致全身性炎症综合征，这在很大程度上是由肿瘤坏死因子α(TNF)的过度表达所介导的。在TTP KO小鼠中，这种表达的增加是肿瘤坏死因子mRNA稳定的次要原因，这一发现导致了TTP作为一种mRNA结合蛋白的特征，它可以促进从选定的mRNAs中移除Poly(A)尾巴，并促进其核溶解破坏。在转基因细胞的过度表达研究中，其他人类家族成员的行为类似于TTP，但基因干扰实验表明，它们参与了不同的生理过程。在目前的研究中，我们开发了一种针对所有三个人类家庭成员的实时聚合酶链式反应分析方法，允许在相同的组织和细胞中对所有三个家庭成员进行比较测量。我们用这种方法定量了所有三种转录本在各种正常人类组织中的表达水平，以及在“NCI 60”中的表达水平，“NCI 60”是一组具有良好特征的人类肿瘤细胞系。尽管对来自基因敲除小鼠的成纤维细胞和巨噬细胞的研究未能证明这些家族成员在转录水平上的代偿性表达，但在某些生理或病理情况下，不同的家族成员仍有可能发挥“TTP等价物”的作用。(C)2007年，爱思唯尔公司出版。
The tristetraprolin (TTP) family of tandem zinc finger proteins comprises three members in man and most other mammals, with a fourth expressed in rodents. In mice, gene disruption of TTP itself leads to a systemic inflammatory syndrome that is mediated in large part by over-expression of tumor necrosis factor alpha (TNF). This increased expression is secondary to stabilization of the TNF mRNA in the TTP KO mice, a finding that led to the characterization of TTP as an mRNA binding protein that can promote the removal of the poly(A) tail from selected mRNAs and facilitate their nucleolytic destruction. The other human family members behave similarly to TTP in over-expression studies of transfected cells, but gene disruption experiments have implicated them in different physiological processes. In the present study, we developed a real-time PCR assay for all three human family members that allowed for comparative measurements of all three family members in the same tissues and cells. We used this assay to quantitate expression levels of all three transcripts in a variety of normal human tissues, as well as in the "NCI 60", a well characterized panel of human tumor cell lines. Although studies in fibroblasts and macrophages derived from knockout mice have failed to demonstrate compensatory expression of the family members in terms of transcript levels, it remains possible that the different family members can function as "TTP equivalents" in certain physiological or pathological circumstances. (C) 2007 Published by Elsevier Inc.