ArticleProceedings of the National Academy of Sciences of the United States of America2003
Designed FHIT alleles establish that Fhit-induced apoptosis in cancer cells is limited by substrate binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 73 citations in OpenAlex.
- Fragile histidine triad (FHIT) suppresses gastric cancer via translational regulation of the epigenetic modifier KDM6B.The Journal of biological chemistry · 2026Article
- Integrated analysis ofCell cycle (Georgetown, Tex.) · 2024Review
- The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.Cells · 2023Article
- The Tumour Suppressor Fhit Protein Activates C-Raf Ubiquitination and Degradation in Human Melanoma Cells by Interacting with Hsp90.Biomedicines · 2022Article
- Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor ApJournal of the American Chemical Society · 2022Article
- Fungicidal Activity of Recombinant Javanicin againstMolecules (Basel, Switzerland) · 2021Article
- Tanshinones induce tumor cell apoptosis via directly targeting FHIT.Scientific reports · 2021Article
- Fhit-Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells.Cell death & disease · 2019Article
- Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.PLoS genetics · 2016Review
- Article
- A Fhit-mimetic peptide suppresses annexin A4-mediated chemoresistance to paclitaxel in lung cancer cells.Oncotarget · 2016Article
- Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis.Cancers · 2014Article
- A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1.Cell cycle (Georgetown, Tex.) · 2014Article
- Activation state-dependent interaction between Gαq subunits and the Fhit tumor suppressor.Cell communication and signaling : CCS · 2013Article
- Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel.PloS one · 2013Article
- Characterization of the role of Fhit in suppression of DNA damage.Advances in biological regulation · 2013Article
- Hits, Fhits and Nits: beyond enzymatic function.Advances in enzyme regulation · 2011Review
- Fragile histidine triad protein: structure, function, and its association with tumorogenesis.Journal of cancer research and clinical oncology · 2010Review
- Fhit regulates invasion of lung tumor cells.Oncogene · 2010Article
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The FHIT gene is inactivated early in the development of many human tumors, and Fhit-deficient mice have increased cancer incidence. Viral reexpression of Fhit kills Fhit-deficient cells by induction of apoptosis. Fhit, a member of branch 2 of the histidine-triad superfamily of nucleoside monophosphate hydrolases and transferases, is a diadenosine polyphosphate hydrolase, the active-site histidine of which is not required for tumor suppression. To provide a rigorous test of the hypothesis that Fhit function depends on forming a complex with substrates, we designed a series of alleles of Fhit intended to reduce substrate-binding andor hydrolytic rates, characterized these mutants biochemically, and then performed quantitative cell-death assays on cancer cells virally infected with each allele. The allele series covered defects as great as 100,000-fold in k(cat) and increases as large as 30-fold in K(M). Nonetheless, when mutant FHIT genes were expressed in two human cancer cell lines containing FHIT deletions, reductions in apoptotic activity correlated exclusively with K(M). Mutants with 2- and 7-fold increases in K(M) significantly reduced apoptotic indices, whereas the mutant with a 30-fold increase in K(M) retained little cellular function. These data indicate that the proapoptotic function of Fhit is limited by substrate binding and is unrelated to substrate hydrolysis.
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Registered trials
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.