核仁蛋白PinX1p通过将端粒酶的蛋白质催化亚基隔离在缺乏端粒酶RNA的无活性复合物中来调节端粒酶。
Nucleolar protein PinX1p regulates telomerase by sequestering its protein catalytic subunit in an inactive complex lacking telomerase RNA.
作者信息
Lin Jue, Blackburn Elizabeth H
机构信息
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-2200, USA.
出版信息
Genes Dev. 2004 Feb 15;18(4):387-96. doi: 10.1101/gad.1171804. Epub 2004 Feb 20.
Abstract
Human TRF1-binding protein PinX1 inhibits telomerase activity. Here we report that overexpression of yeast PinX1p (yPinX1p) results in shortened telomeres and decreased in vitro telomerase activity. yPinX1p coimmunoprecipitated with yeast telomerase protein Est2p even in cells lacking the telomerase RNA TLC1, or the telomerase-associated proteins Est1p and Est3p. Est2p regions required for binding to yPinX1p or TLC1 were similar. Furthermore, we found two distinct Est2p complexes exist, containing either yPinX1p or TLC1. Levels of Est2p-yPinX1p complex increased when TLC1 was deleted and decreased when TLC1 was overexpressed. Hence, we propose that yPinX1p regulates telomerase by sequestering its protein catalytic subunit in an inactive complex lacking telomerase RNA.
摘要
人类TRF1结合蛋白PinX1可抑制端粒酶活性。在此我们报告，酵母PinX1p（yPinX1p）的过表达导致端粒缩短以及体外端粒酶活性降低。即使在缺乏端粒酶RNA TLC1、或端粒酶相关蛋白Est1p和Est3p的细胞中，yPinX1p也能与酵母端粒酶蛋白Est2p进行共免疫沉淀。与yPinX1p或TLC1结合所需的Est2p区域相似。此外，我们发现存在两种不同的Est2p复合物，分别含有yPinX1p或TLC1。当TLC1缺失时，Est2p - yPinX1p复合物水平增加；而当TLC1过表达时，其水平降低。因此，我们提出yPinX1p通过将其蛋白质催化亚基隔离在缺乏端粒酶RNA的无活性复合物中来调节端粒酶。
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本文引用的文献
1
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Trends Cell Biol. 2003 Jun;13(6):289-94. doi: 10.1016/s0962-8924(03)00085-0.
2
Telomerase: what are the Est proteins doing?端粒酶：Est蛋白在做什么？
Curr Opin Cell Biol. 2003 Jun;15(3):275-80. doi: 10.1016/s0955-0674(03)00040-1.
3
Developmentally programmed gene elimination in Euplotes crassus facilitates a switch in the telomerase catalytic subunit.粗尾真核生物中发育编程的基因消除促进了端粒酶催化亚基的转换。
Cell. 2003 May 30;113(5):565-76. doi: 10.1016/s0092-8674(03)00363-5.
4
Distinct biogenesis pathways for human telomerase RNA and H/ACA small nucleolar RNAs.人类端粒酶RNA和H/ACA小核仁RNA的独特生物合成途径。
Mol Cell. 2003 May;11(5):1361-72. doi: 10.1016/s1097-2765(03)00196-5.
5
POT1 as a terminal transducer of TRF1 telomere length control.POT1作为TRF1端粒长度控制的终端转导分子。
Nature. 2003 Jun 26;423(6943):1013-8. doi: 10.1038/nature01688. Epub 2003 May 25.
6
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Genes Dev. 2003 May 1;17(9):1078-83. doi: 10.1101/gad.1060803.
7
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Mol Biol Cell. 2003 Jan;14(1):1-13. doi: 10.1091/mbc.e02-06-0327.
8
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9
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10
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