ArticleThe Journal of biological chemistry2010
CHIP promotes human telomerase reverse transcriptase degradation and negatively regulates telomerase activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 80 citations in OpenAlex.
- STUB1 downregulates TOP2A through a dual mechanism of ubiquitination and FOXM1-mediated transcription repression, suppressing breast cancer growth and enhancing sensitivity to chemotherapy.Cellular & molecular biology letters · 2026Article
- H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 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
- TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection.International journal of molecular sciences · 2023Article
- The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells.Oncology research · 2023Article
- Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies.International journal of molecular sciences · 2022Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.Molecules and cells · 2021Article
- The Connection Between Cell Fate and Telomere.Advances in experimental medicine and biology · 2021Review
- Telomere Maintenance Pathway Activity Analysis Enables Tissue- and Gene-Level Inferences.Frontiers in genetics · 2021Article
- Telomerase Biogenesis and Activities from the Perspective of Its Direct Interacting Partners.Cancers · 2020Review
- Telomere-related Markers for Cancer.Current topics in medicinal chemistry · 2020Review
- Identification of a TRBD zinc finger-interacting protein in Giardia duodenalis and its regulation of telomerase.Parasites & vectors · 2019Article
- Diverse regulatory manners of human telomerase reverse transcriptase.Cell communication and signaling : CCS · 2019Review
- The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism.Scientific reports · 2019Article
- Identifying term relations cross different gene ontology categories.BMC bioinformatics · 2017Article
- Tandem affinity purification of AtTERT reveals putative interaction partners of plant telomerase in vivo.Protoplasma · 2017Article
- Heat Shock Protein 90 Ensures Efficient Mumps Virus Replication by Assisting with Viral Polymerase Complex Formation.Journal of virology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The maintenance of eukaryotic telomeres requires telomerase, which is minimally composed of a telomerase reverse transcriptase (TERT) and an associated RNA component. Telomerase activity is tightly regulated by expression of human (h) TERT at both the transcriptional and post-translational levels. The Hsp90 and p23 molecular chaperones have been shown to associate with hTERT for the assembly of active telomerase. Here, we show that CHIP (C terminus of Hsc70-interacting protein) physically associates with hTERT in the cytoplasm and regulates the cellular abundance of hTERT through a ubiquitin-mediated degradation. Overexpression of CHIP prevents nuclear translocation of hTERT and promotes hTERT degradation in the cytoplasm, thereby inhibiting telomerase activity. In contrast, knockdown of endogenous CHIP results in the stabilization of cytoplasmic hTERT. However, it does not affect the level of nuclear hTERT and has no effect on telomerase activity and telomere length. We further show that the binding of CHIP and Hsp70 to hTERT inhibits nuclear translocation of hTERT by dissociating p23. However, Hsp90 binding to hTERT was not affected by CHIP overexpression. These results suggest that CHIP can remodel the hTERT-chaperone complexes. Finally, the amount of hTERT associated with CHIP peaks in G(2)/M phases but decreases during S phase, suggesting a cell cycle-dependent regulation of hTERT. Our data suggest that CHIP represents a new pathway for modulating telomerase activity in cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.