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PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells.
Hsieh, Meng-Hsun; Chen, Yi-Ting; Chen, You-Tzung; Lee, Yi-Hsuan; Lu, Jean; Chien, Chung-Liang; Chen, Hsin-Fu; Ho, Hong-Nerng; Yu, Chia-Jung; Wang, Zhao-Qi; Teng, Shu-Chun.
Afiliação
  • Hsieh MH; Department of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Chen YT; Department of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Chen YT; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Lee YH; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
  • Lu J; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
  • Chien CL; Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Chen HF; Department of Obstetrics and Gynecology and Institute of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Ho HN; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Yu CJ; Department of Obstetrics and Gynecology and Institute of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Wang ZQ; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Teng SC; Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
Nucleic Acids Res ; 45(18): 10492-10503, 2017 Oct 13.
Article em En | MEDLINE | ID: mdl-28985359
ABSTRACT
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Krüppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs. Recruitment of KLF4 to TERT promoter is reduced in PARP1-suppressed cells. The poly(ADP-ribose) polymerase activity is dispensable, while the oligo(ADP-ribose) polymerase activity is required for the PARP1- and KLF4-mediated TERT activation. Repression of Parp1 in mouse ESCs decreases expression of pluripotent markers and induces differentiation. These results suggest that PARP1 recruits KLF4 to activate telomerase expression and stem cell pluripotency, indicating a positive regulatory role of the PARP1-KLF4 complex in telomerase expression in cancer and stem cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Telomerase / Fatores de Transcrição Kruppel-Like / Células-Tronco Embrionárias / Poli(ADP-Ribose) Polimerase-1 / Neoplasias Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Telomerase / Fatores de Transcrição Kruppel-Like / Células-Tronco Embrionárias / Poli(ADP-Ribose) Polimerase-1 / Neoplasias Idioma: En Ano de publicação: 2017 Tipo de documento: Article