ArticleCancer research2008
Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- RNA interacts with topoisomerase I to adjust DNA topology.Molecular cell · 2024Article
- G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity.Nucleic acids research · 2024Article
- Evidence of direct interaction between cisplatin and the caspase-cleaved prostate apoptosis response-4 tumor suppressor.Protein science : a publication of the Protein Society · 2024Article
- Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells.Cancers · 2022Article
- Prostate apoptosis response-4 and tumor suppression: it's not just about apoptosis anymore.Cell death & disease · 2021Review
- Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity.American journal of physiology. Cell physiology · 2020Article
- pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain.Biomolecules · 2018Article
- Inhibition of Twist1-mediated invasion by Chk2 promotes premature senescence in p53-defective cancer cells.Cell death and differentiation · 2017Article
- A journey beyond apoptosis: new enigma of controlling metastasis by pro-apoptotic Par-4.Clinical & experimental metastasis · 2016Review
- Y-box binding protein 1 enhances DNA topoisomerase 1 activity and sensitivity to camptothecin via direct interaction.Journal of experimental & clinical cancer research : CR · 2014Article
- The tumor suppressor prostate apoptosis response-4 (Par-4) is regulated by mutant IDH1 and kills glioma stem cells.Acta neuropathologica · 2014Article
- Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis.Nature chemical biology · 2014Article
- Cloning, expression, purification, crystallization and preliminary crystallographic analysis of the C-terminal domain of Par-4 (PAWR).Acta crystallographica. Section F, Structural biology communications · 2014Article
- Mechanisms of apoptosis by the tumor suppressor Par-4.Journal of cellular physiology · 2012Review
- Prostate apoptosis response-4 is expressed in normal cholangiocytes, is down-regulated in human cholangiocarcinoma, and promotes apoptosis of neoplastic cholangiocytes when induced pharmacologically.The American journal of pathology · 2010Article
- Immobilizing topoisomerase I on a surface plasmon resonance biosensor chip to screen for inhibitors.Journal of biomedical science · 2010Article
- Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network.Molecular cancer · 2010Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The regulation of DNA relaxation by topoisomerase 1 (TOP1) is essential for DNA replication, transcription, and recombination events. TOP1 activity is elevated in cancer cells, yet the regulatory mechanism restraining its activity is not understood. We present evidence that the tumor suppressor protein prostate apoptosis response-4 (Par-4) directly binds to TOP1 and attenuates its DNA relaxation activity. Unlike camptothecin, which binds at the TOP1-DNA interface to form cleavage complexes, Par-4 interacts with TOP1 via its leucine zipper domain and sequesters TOP1 from the DNA. Par-4 knockdown by RNA interference enhances DNA relaxation and gene transcription activities and promotes cellular transformation in a TOP1-dependent manner. Conversely, attenuation of TOP1 activity either by RNA interference or Par-4 overexpression impedes DNA relaxation, cell cycle progression, and gene transcription activities and inhibits transformation. Collectively, our findings suggest that Par-4 serves as an intracellular repressor of TOP1 catalytic activity and regulates DNA topology to suppress cellular transformation.
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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.