PES1 is a critical component of telomerase assembly and regulates cellular senescence
PES1 is a critical component of telomerase assembly and regulates cellular senescence
复制标题
PES1 是端粒酶组装的关键成分并调节细胞衰老
DOI：
10.1126/sciadv.aav1090
复制
发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Ye, Qinong
中科院分区：
文献类型：
--
作者：
Cheng, Long;Yuan, Bin;Ye, Qinong
端粒酶通过在染色体末端添加端粒重复DNA来延缓端粒缩短和细胞衰老的发生，其激活有助于致癌。端粒酶主要由端粒酶逆转录酶（TERT）和端粒酶RNA （TR）组成。然而，端粒酶是如何组装的在很大程度上是未知的。在这里，我们证明了PES1 (Pescadillo)，一种在许多癌症中过表达的蛋白质，通过与TERT的直接相互作用，与TERT和TR形成复合物，调节端粒酶活性，端粒长度维持和衰老。PES1不与先前报道的端粒酶成分Reptin、Pontin、p23和Hsp90相互作用。PES1通过促进TERT和TR之间的直接相互作用而不影响TERT和TR水平，从而促进端粒酶的组装。PES1表达与乳腺癌患者端粒酶活性呈正相关，与衰老呈负相关。因此，我们发现了一种以前未知的端粒酶复合物，并且靶向PES1可能为癌症治疗开辟新的途径。
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.