Falkor, a novel cell growth regulator isolated by a functional genetic screen

Falkor, a novel cell growth regulator isolated by a functional genetic screen
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Falkor,一种通过功能基因筛选分离的新型细胞生长调节剂

DOI:
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发表时间:
2002
期刊:
影响因子:
8
通讯作者:
V. Rotter
V. Rotter
中科院分区:
医学1区
文献类型:
--
作者:
Neta Erez;M. Milyavsky;N. Goldfinger;E. Peles;A. Gudkov;V. Rotter

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一种新的细胞生长调节剂,命名为Falkor,是利用哺乳动物基因克隆的功能方法,遗传抑制元件(GSE)的方法。在该筛选中,Falkor的C-末端结构域的表达赋予细胞对顺铂诱导的生长停滞的抗性。Falkor的C-末端,但不是全长蛋白的表达,增强细胞生长后的遗传毒性应力和在正常条件下,这表明该蛋白在细胞生长控制的一般作用。C-末端片段的这种作用被全长Falkor的过表达所消除,这表明该片段抵消了全长蛋白的功能。Falkor由2kb mRNA编码,其在各种组织中以不同水平存在,并且定位于细胞核中。从GSE文库中分离的Falkor的C-末端结构域与已知的人和大鼠细胞生长调节剂SM-20和C. Elegans蛋白EGL-9,最近显示修饰缺氧诱导因子-1 α。同源性表明,这些蛋白质共享一个功能域,是保守的一个家庭的生长调节蛋白。
A novel cell growth regulator, named Falkor, was identified using a functional approach to mammalian gene cloning, the Genetic Supressor Elements (GSE) method. In this screen, expression of the C-terminal domain of Falkor conferred cells with resistance to cisplatin-induced growth arrest. Expression of the C-terminus of Falkor, but not of the full-length protein, enhanced cell growth both following genotoxic stress and under normal conditions suggesting a general role for this protein in cell growth control. This effect of the C-terminus fragment was abrogated by over-expression of the full-length Falkor, suggesting that the fragment counteracts the function of the full-length protein. Falkor is encoded by a 2-kb mRNA which is present at different levels in various tissues, and is localized in the nucleus of cells. The C-terminal domain of Falkor, isolated from the GSE library, has significant homology to a known human and rat cell growth regulator, SM-20, and to the C. elegans protein EGL-9, recently shown to modify the Hypoxia Inducible Factor-1α. The homology suggests that these proteins share a functional domain that is conserved among a family of growth regulation proteins.
DOI: 10.1126/science.282.5393.1497
发表时间: 1998-11-20
期刊: SCIENCE
影响因子: 56.9
作者:
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者: Vogelstein, B