ArticleThe Journal of biological chemistry2011
Telomerase inhibitor PinX1 provides a link between TRF1 and telomerase to prevent telomere elongation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- PinX1 suppresses cancer progression by inhibiting telomerase activity in cervical squamous cell carcinoma and endocervical adenocarcinoma.Genes & diseases · 2025Article
- PinX1 plays multifaceted roles in human cancers: a review and perspectives.Molecular biology reports · 2024Review
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- Post-Transcriptional and Post-Translational Modifications in Telomerase Biogenesis and Recruitment to Telomeres.International journal of molecular sciences · 2023Review
- Telomeres: Implications for Cancer Development.International journal of molecular sciences · 2018Review
- NF-κB potentiates tumor growth by suppressing a novel target LPTS.Cell communication and signaling : CCS · 2017Article
- PinX1: structure, regulation and its functions in cancer.Oncotarget · 2016Review
- New prospects for targeting telomerase beyond the telomere.Nature reviews. Cancer · 2016Review
- Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes.World journal of gastroenterology · 2016Review
- Polo-like Kinase 1 (Plk1) Up-regulates Telomerase Activity by Affecting Human Telomerase Reverse Transcriptase (hTERT) Stability.The Journal of biological chemistry · 2015Article
- Zscan4 interacts directly with human Rap1 in cancer cells regardless of telomerase status.Cancer biology & therapy · 2014Article
- The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis.Nucleic acids research · 2014Article
- 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.The Journal of biological chemistry · 2014Article
- Reduced expression of PinX1 correlates to progressive features in patients with prostate cancer.Cancer cell international · 2014Article
- The role of PinX1 in growth control of breast cancer cells and its potential molecular mechanism by mRNA and lncRNA expression profiles screening.BioMed research international · 2014Article
- Nuclear condensation and cell cycle arrest induced by telomerase siRNA in neuroblastoma cells.Journal of neuro-oncology · 2013Article
- TIN2 stability is regulated by the E3 ligase Siah2.Molecular and cellular biology · 2012Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Telomere maintenance is essential for protecting chromosome ends. Aberrations in telomere length have been implicated in cancer and aging. Telomere elongation by human telomerase is inhibited in cis by the telomeric protein TRF1 and its associated proteins. However, the link between TRF1 and inhibition of telomerase elongation of telomeres remains elusive because TRF1 has no direct effect on telomerase activity. We have previously identified one Pin2/TRF1-interacting protein, PinX1, that has the unique property of directly binding and inhibiting telomerase catalytic activity (Zhou, X. Z., and Lu, K. P. (2001) Cell 107, 347-359). However, nothing is known about the role of the PinX1-TRF1 interaction in the regulation of telomere maintenance. By identifying functional domains and key amino acid residues in PinX1 and TRF1 responsible for the PinX1-TRF1 interaction, we show that the TRF homology domain of TRF1 interacts with a minimal 20-amino acid sequence of PinX1 via hydrophilic and hydrophobic interactions. Significantly, either disrupting this interaction by mutating the critical Leu-291 residue in PinX1 or knocking down endogenous TRF1 by RNAi abolishes the ability of PinX1 to localize to telomeres and to inhibit telomere elongation in cells even though neither has any effect on telomerase activity per se. Thus, the telomerase inhibitor PinX1 is recruited to telomeres by TRF1 and provides a critical link between TRF1 and telomerase inhibition to prevent telomere elongation and help maintain telomere homeostasis.
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