PES1 is a critical component of telomerase assembly and regulates cellular senescence.

Abstract	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.
Authors	Long Cheng, Bin Yuan, Sunyang Ying, Chang Niu, Hongxu Mai, Xin Guan, Xiaohui Yang, Yan Teng, Jing Lin, Junjian Huang, Rui Jin, Jun Wu, Bo Liu, Shaohong Chang, Enqun Wang, Chunxia Zhang, Ning Hou, Xuan Cheng, Danyang Xu, Xiao Yang, Shan Gao, Qinong Ye
Journal	Science advances (Sci Adv) Vol. 5 Issue 5 Pg. eaav1090 (05 2019) ISSN: 2375-2548 [Electronic] United States
PMID	31106266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins PES1 protein, human Pes1 protein, mouse RNA, Small Interfering RNA-Binding Proteins TERT protein, human Telomerase Tert protein, mouse
Topics	Animals Apoptosis Breast Neoplasms (metabolism) Cell Cycle Cell Line, Tumor Cellular Senescence DNA-Binding Proteins (metabolism) Fibroblasts (metabolism) Gene Expression Profiling Gene Expression Regulation, Neoplastic HEK293 Cells Hep G2 Cells Humans MCF-7 Cells Mice Mice, Knockout Protein Binding RNA, Small Interfering (metabolism) RNA-Binding Proteins (metabolism) Telomerase (metabolism) Telomere (ultrastructure)

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