[Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells].
[Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells].
复制标题
[凋亡核酸内切酶EndoG诱导端粒酶催化亚基hTERT的选择性剪接和肿瘤细胞死亡]。
DOI：
--
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
N. Sokolov
中科院分区：
文献类型：
--
作者：
D. Zhdanov;D. A. Vasina;V. Orlova;V. Y. Gotovtseva;M. Bibikova;V. Pokrovsky;M. Pokrovskaya;S. Aleksandrova;N. Sokolov
端粒酶活性是由端粒酶催化亚基hTERT（human Telomerase Reverse Transcriptase）mRNA的选择性剪接调控的。非活性剪接hTERT的诱导导致端粒酶活性的抑制。然而，很少有人知道hTERTmRNA选择性剪接的机制。本研究的目的是确定凋亡内切酶EndoG在hTERT选择性剪接和端粒酶活性中的作用。在12个结肠癌细胞系中发现EndoG和hTERT剪接变体的表达之间存在强相关性。EndoG过表达下调hTERT活性全长变体的表达，上调hTERT非活性剪接变体的表达。全长hTERT的减少导致端粒酶活性下调，细胞分裂过程中端粒长度显著缩短，细胞进入复制性衰老状态，激活凋亡，最终导致细胞死亡。提示EndoG参与了端粒酶催化亚单位mRNA的选择性剪接，调节端粒酶活性和细胞命运。
Telomerase activity is known to be regulated by alternative splicing of its catalytic subunit hTERT (human Telomerase Reverse Transcriptase) mRNA. Induction of non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. Strong correlation was found between expression of EndoG and hTERT splice-variants in 12 colon cancer cell lines. Overexpression of EndoG in СаСо-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, dramatically shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. These data indicated the participation of EndoG in alternative splicing of mRNA of telomerase catalytic subunit, regulation of telomerase activity and cell fate.
登录
查看更多内容
影响因子：
3.5
作者：
Daniel M;Peek GW;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
14.9
作者：
Cawthon, RM
通讯作者：
Cawthon, RM
影响因子：
56.9
作者：
KIM, NW;PIATYSZEK, MA;SHAY, JW
通讯作者：
SHAY, JW
影响因子：
3.7
作者：
Basnakian, Alexei G.;Apostolov, Eugene O.;Shah, Sudhir V.
通讯作者：
Shah, Sudhir V.
EndoG 对凋亡核酸内切酶的调节。
影响因子：
3.1
作者：
Zhdanov,DmitryD;Fahmi,Tariq;Wang,Xiaoying;Apostolov,EugeneO;Sokolov,NikolaiN;Javadov,Sabzali;Basnakian,AlexeiG
通讯作者：
Basnakian,AlexeiG