skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line

Abstract

Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely hasmore » the specific mechanism yet to be defined.« less

Authors:
 [1];  [1]; ;  [1];  [2];  [1]
  1. Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan (China)
  2. Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou (China)
Publication Date:
OSTI Identifier:
22416303
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 445; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL RADIATION EFFECTS; HUMAN POPULATIONS; INHIBITION; MAINTENANCE; OSTEOSARCOMAS; PHENOTYPE; PROTEINS; RADIOSENSITIVITY; REGULATIONS; TELOMERES

Citation Formats

Qiang, Weiguang, Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Wu, Qinqin, Department of Radiation Oncology, Changzhou Tumor Hospital, Soochow University, Changzhou, Zhou, Fuxiang, Xie, Conghua, Wu, Changping, and Zhou, Yunfeng. Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.02.001.
Qiang, Weiguang, Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Wu, Qinqin, Department of Radiation Oncology, Changzhou Tumor Hospital, Soochow University, Changzhou, Zhou, Fuxiang, Xie, Conghua, Wu, Changping, & Zhou, Yunfeng. Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line. United States. https://doi.org/10.1016/J.BBRC.2014.02.001
Qiang, Weiguang, Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Wu, Qinqin, Department of Radiation Oncology, Changzhou Tumor Hospital, Soochow University, Changzhou, Zhou, Fuxiang, Xie, Conghua, Wu, Changping, and Zhou, Yunfeng. 2014. "Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line". United States. https://doi.org/10.1016/J.BBRC.2014.02.001.
@article{osti_22416303,
title = {Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line},
author = {Qiang, Weiguang and Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou and Wu, Qinqin and Department of Radiation Oncology, Changzhou Tumor Hospital, Soochow University, Changzhou and Zhou, Fuxiang and Xie, Conghua and Wu, Changping and Zhou, Yunfeng},
abstractNote = {Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.},
doi = {10.1016/J.BBRC.2014.02.001},
url = {https://www.osti.gov/biblio/22416303}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 445,
place = {United States},
year = {Fri Mar 07 00:00:00 EST 2014},
month = {Fri Mar 07 00:00:00 EST 2014}
}