ULK1 inhibition attenuates telomerase activity in hepatic cells

被引:2
|
作者
Raza, Sana [1 ]
Rajak, Sangam [1 ]
Srivastava, Jyotika [2 ]
Tewari, Archana [1 ]
Gupta, Pratima [1 ]
Chakravarti, Bandana [1 ]
Ghosh, Sujoy [3 ]
Chaturvedi, Chandra P. [2 ]
Sinha, Rohit A. [1 ]
机构
[1] Sanjay Gandhi Postgrad Inst Med Sci, Dept Endocrinol, Lucknow, Uttar Pradesh, India
[2] Sanjay Gandhi Postgrad Inst Med Sci, Dept Hematol, Stem Cell Res Facil, Lucknow, Uttar Pradesh, India
[3] Duke NUS Med Sch, Ctr Computat Biol, Singapore, Singapore
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2022年 / 1869卷 / 12期
关键词
SENESCENCE; AUTOPHAGY;
D O I
10.1016/j.bbamcr.2022.119355
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autophagy and telomere maintenance are two cellular survival processes that show a strong correlation during human ageing and cancer growth, however, their causal relationship remains unclear. In this study, using an unbiased transcriptomics approach, we uncover a novel role of autophagy genes in regulating telomere extension and maintenance pathways. Concomitantly, the pharmacological inhibition of ULK1 (Unc-51 like autophagy activating kinase 1) attenuated human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity in HepG2 cells. Furthermore, the suppression of telomerase activity upon ULK1 inhibition was associated with telomere shortening and onset of cellular senescence in HepG2 cells. These results, thus, demonstrate a direct role of autophagy in maintaining cellular longevity via regulation of telomerase activity, which may have implications in the pathophysiology of ageing and cancers.
引用
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页数:4
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