1. PES1 is a critical component of telomerase assembly and regulates cellular senescence
- Author
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Chunxia Zhang, Rui Jin, Jing Lin, Shan Gao, Hong-xu Mai, Ning Hou, Junjian Huang, Danyang Xu, Qinong Ye, Yan Teng, Xin Guan, Bin Yuan, Enqun Wang, Sunyang Ying, Xiao Yang, Long Cheng, Jun Wu, Chang Niu, Xuan Cheng, Xiaohui Yang, Shaohong Chang, and Bo Liu
- Subjects
Senescence ,Telomerase ,Apoptosis ,Breast Neoplasms ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Telomerase reverse transcriptase ,RNA, Small Interfering ,Molecular Biology ,Cellular Senescence ,Research Articles ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Multidisciplinary ,Chemistry ,Gene Expression Profiling ,Cell Cycle ,RNA ,RNA-Binding Proteins ,SciAdv r-articles ,Hep G2 Cells ,Cell Biology ,Cell cycle ,Fibroblasts ,Telomere ,Cell biology ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Carcinogenesis ,DNA ,Protein Binding ,Research Article - Abstract
PES1 is a new component of telomerase assembly that regulates telomerase activity, telomere length, and cellular senescence., Telomerase defers the onset of telomere shortening and cellular senescence by adding telomeric repeat DNA to chromosome ends, and its activation contributes to carcinogenesis. Telomerase minimally consists of the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR). However, how telomerase assembles is largely unknown. Here, we demonstrate that PES1 (Pescadillo), a protein overexpressed in many cancers, forms a complex with TERT and TR through direct interaction with TERT, regulating telomerase activity, telomere length maintenance, and senescence. PES1 does not interact with the previously reported telomerase components Reptin, Pontin, p23, and Hsp90. PES1 facilitates telomerase assembly by promoting direct interaction between TERT and TR without affecting TERT and TR levels. PES1 expression correlates positively with telomerase activity and negatively with senescence in patients with breast cancer. Thus, we identify a previously unknown telomerase complex, and targeting PES1 may open a new avenue for cancer therapy.
- Published
- 2019