2 350

Cited 14 times in

PinX1, a Telomere Repeat-binding Factor 1 (TRF1)-interacting Protein, Maintains Telomere Integrity by Modulating TRF1 Homeostasis, the Process in Which Human Telomerase Reverse Transcriptase (hTERT) Plays Dual Roles

Authors
 Jeong Eun Yoo  ;  Young Nyun Park  ;  Bong-Kyeong Oh 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(10) : 6886-6898, 2014 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2014
MeSH
HeLa Cells ; Humans ; Protein Stability ; Telomerase/genetics ; Telomerase/physiology* ; Telomere/genetics ; Telomere/physiology* ; Telomere Homeostasis/genetics ; Telomere Homeostasis/physiology* ; Telomeric Repeat Binding Protein 1/chemistry ; Telomeric Repeat Binding Protein 1/metabolism* ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/physiology*
Keywords
Chromosomal Instability ; DNA Damage Response ; TERT ; Telomerase ; Telomere Deficiency ; Telomeres ; Telomeric Repeat-binding Factor 1 ; Tumor Cell Biology ; Tumor Suppressor Gene
Abstract
TRF1, a telomere-binding protein, is important for telomere protection and homeostasis. PinX1 interacts with TRF1, but the physiological consequences of their interaction in telomere protection are not yet understood. Here we investigated PinX1 function on TRF1 stability in HeLa cells. PinX1 overexpression stabilized TRF1, but PinX1 depletion by siRNA led to TRF1 degradation, TRF1 ubiquitination, and less TRF1 telomere association. The depletion also induced DNA damage responses at telomeres and chromosome instability. These telomere dysfunctional phenotypes were in fact due to TRF1 deficiency. We also report that hTERT, a catalytic component of telomerase, plays dual roles in the TRF1 steady state pathway. PinX1-mediated TRF1 stability was not observed in hTERT-negative immortal cells, but was pronounced when hTERT was ectopically expressed in the cells, suggesting that hTERT may be needed in the PinX1-mediated TRF1 stability pathway. Interestingly, the knockdown of both PinX1 and hTERT in HeLa cells stabilized TRF1, suppressed DNA damage response activation, and restored chromosome stability. In summary, our findings suggested that PinX1 may maintain telomere integrity by regulating TRF1 stability and that hTERT may act as both a positive and a negative regulator of TRF1 homeostasis in a PinX1-dependent manner.
Full Text
http://www.jbc.org/content/289/10/6886.long
DOI
10.1074/jbc.M113.506006
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98260
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links