共查询到20条相似文献,搜索用时 62 毫秒
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Dyskerin binds the H/ACA box of human telomerase RNA and is a core telomerase subunit required for RNP biogenesis and enzyme function in vivo. Missense mutations in dyskerin result in dyskeratosis congenita, a complex syndrome characterized by bone marrow failure, telomerase enzyme deficiency, and progressive telomere shortening. Here we demonstrate that dyskerin also contributes to telomere maintenance in Arabidopsis thaliana. We report that both AtNAP57, the Arabidopsis dyskerin homolog, and AtTERT, the telomerase catalytic subunit, accumulate in the plant nucleolus, and AtNAP57 associates with active telomerase RNP particles in an RNA-dependent manner. Furthermore, AtNAP57 interacts in vitro with AtPOT1a, a novel component of Arabidopsis telomerase. Although a null mutation in AtNAP57 is lethal, AtNAP57, like AtTERT, is not haploinsufficient for telomere maintenance in Arabidopsis. However, introduction of an AtNAP57 allele containing a T66A mutation decreased telomerase activity in vitro, disrupted telomere length regulation on individual chromosome ends in vivo, and established a new, shorter telomere length set point. These results imply that T66A NAP57 behaves as a dominant-negative inhibitor of telomerase. We conclude that dyskerin is a conserved component of the telomerase RNP complex in higher eukaryotes that is required for maximal enzyme activity in vivo. 相似文献
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Xiong J Fan S Meng Q Schramm L Wang C Bouzahza B Zhou J Zafonte B Goldberg ID Haddad BR Pestell RG Rosen EM 《Molecular and cellular biology》2003,23(23):8668-8690
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Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells 总被引:3,自引:0,他引:3
Doshida M Ohmichi M Tsutsumi S Kawagoe J Takahashi T Du B Mori-Abe A Ohta T Saitoh-Sekiguchi M Takahashi K Kurachi H 《The Journal of biological chemistry》2006,281(34):24270-24278
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Pro-atherogenic factors induce telomerase inactivation in endothelial cells through an Akt-dependent mechanism 总被引:8,自引:0,他引:8
Advanced aging may contribute to impairment of angiogenesis and development of vascular diseases. Telomerase was shown to delay endothelial cell (EC) senescence. Therefore, we determined the regulation of telomerase activity in EC. Inhibition of phosphoinositol 3-kinase (PI3K) suppressed telomerase activity, whereas inhibitors directed against ERK1/2 or protein kinase C had no effect. Dominant negative Akt significantly reduced telomerase activity. Moreover, pro-atherogenic stimuli such as oxidized low density lipoprotein led to an inactivation of Akt and diminished telomerase activity. Thus, the PI3K/Akt pathway plays an important role in the regulation of telomerase activity. Pro-atherosclerotic factors impair telomerase activity and thereby may promote EC aging. 相似文献
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Determinants in mammalian telomerase RNA that mediate enzyme processivity and cross-species incompatibility
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Telomerase contains two essential components: an RNA molecule that templates telomeric repeat synthesis and a catalytic protein component. Human telomerase is processive, while the mouse enzyme has much lower processivity. We have identified nucleotide determinants in the telomerase RNA that are responsible for this difference in processivity. Mutations adjacent to the template region of human and mouse telomerase RNA significantly altered telomerase processivity both in vitro and in vivo. We also identified functionally important nucleotides in the pseudoknot domain of telomerase RNA that potentially mediate the incompatibility between human TERT and mouse telomerase RNA. These experiments identify essential residues of the telomerase RNA that regulate telomerase activity and processivity. 相似文献
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