scholarly journals HuB and HuD repress telomerase activity by dissociating HuR from TERC

2021 ◽  
Author(s):  
Xiaolei Cheng ◽  
Xiaoping Gu ◽  
Tianjiao Xia ◽  
Zhengliang Ma ◽  
Zhongzhou Yang ◽  
...  

Abstract The ubiquitous RNA-binding protein HuR (ELAVL1) promotes telomerase activity by associating with the telomerase noncoding RNA TERC. However, the role of the neural-specific members HuB, HuC, and HuD (ELAVL2–4) in telomerase activity is unknown. Here, we report that HuB and HuD, but not HuC, repress telomerase activity in human neuroblastoma cells. By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT–TERC core complex. Furthermore, HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previously shown to enhance telomerase activity to promote cell growth. Our findings reveal a novel mechanism controlling telomerase activity in human neuroblastoma cells that involves a competition between HuR and the related, neural-specific proteins HuB and HuD.

2014 ◽  
Vol 1575 ◽  
pp. 12-21 ◽  
Author(s):  
Xinyi Yang ◽  
Bin Wang ◽  
Hongqiang Zeng ◽  
Chunqing Cai ◽  
Qiansheng Hu ◽  
...  

2009 ◽  
Vol 20 (7) ◽  
pp. 2041-2048 ◽  
Author(s):  
Petra Obexer ◽  
Judith Hagenbuchner ◽  
Thomas Unterkircher ◽  
Nora Sachsenmaier ◽  
Christoph Seifarth ◽  
...  

The phosphatidylinositol 3-kinase (PI3K)–protein kinase B (PKB) pathway regulates survival and chemotherapy resistance of neuronal cells, and its deregulation in neuroblastoma (NB) tumors predicts an adverse clinical outcome. Here, we show that inhibition of PI3K-PKB signaling in human NB cells induces nuclear translocation of FOXO3/FKHRL1, represses the prosurvival protein BIRC5/Survivin, and sensitizes to DNA-damaging agents. To specifically address whether FKHRL1 contributes to Survivin regulation, we introduced a 4-hydroxy-tamoxifen-regulated FKHRL1(A3)ERtm allele into NB cells. Conditional FKHRL1 activation repressed Survivin transcription and protein expression. Transgenic Survivin exerted a significant antiapoptotic effect and prevented the accumulation of Bim and Bax at mitochondria, the loss of mitochondrial membrane potential as well as the release of cytochrome c during FKHRL1-induced apoptosis. In concordance, Survivin knockdown by retroviral short hairpin RNA technology accelerated FKHRL1-induced apoptosis. Low-dose activation of FKHRL1 sensitized to the DNA-damaging agents doxorubicin and etoposide, whereas the overexpression of Survivin diminished FKHRL1 sensitization to these drugs. These results suggest that repression of Survivin by FKHRL1 facilitates FKHRL1-induced apoptosis and sensitizes to cell death induced by DNA-damaging agents, which supports the central role of PI3K-PKB-FKHRL1 signaling in drug resistance of human NB.


2009 ◽  
Vol 108 (6) ◽  
pp. 1434-1441 ◽  
Author(s):  
Hyun-Pil Lee ◽  
Xiaochun Zhu ◽  
Xiongwei Zhu ◽  
S. Chad Skidmore ◽  
George Perry ◽  
...  

1991 ◽  
Vol 19 (4) ◽  
pp. 424S-424S ◽  
Author(s):  
DAVID G. LAMBERT ◽  
RICHARD J. H. WOJCIKIEWICZ ◽  
STEFAN R. NAHORSKI

2013 ◽  
Vol 7 (Suppl 3) ◽  
pp. S11 ◽  
Author(s):  
Arsen O Batagov ◽  
Aliaksandr A Yarmishyn ◽  
Piroon Jenjaroenpun ◽  
Jovina Z Tan ◽  
Yuichiro Nishida ◽  
...  

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