ArticleProceedings of the National Academy of Sciences of the United States of America1998
Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- 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
- Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor ApJournal of the American Chemical Society · 2022Article
- Re-evaluation of Diadenosine Tetraphosphate (ApFrontiers in molecular biosciences · 2020Review
- Second messenger ApNature communications · 2019Article
- Sedoheptulose-1,7-bisphospate Accumulation and Metabolic Anomalies in Hepatoma Cells Exposed to Oxidative Stress.Oxidative medicine and cellular longevity · 2019Article
- Impact of FHIT loss on the translation of cancer-associated mRNAs.Molecular cancer · 2017Article
- Identification of Fhit as a post-transcriptional effector of Thymidine Kinase 1 expression.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- A Fhit-mimetic peptide suppresses annexin A4-mediated chemoresistance to paclitaxel in lung cancer cells.Oncotarget · 2016Article
- Immunohistochemical characterization of FHIT expression in normal human tissues.Interventional medicine & applied science · 2016Article
- Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ.BMC cancer · 2015Article
- 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
- Structural characterization of human histidine triad nucleotide-binding protein 2, a member of the histidine triad superfamily.The FEBS journal · 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
- Crystallization and preliminary X-ray analysis of the diadenosine 5',5'''-P1,P4-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.Acta crystallographica. Section F, Structural biology and crystallization communications · 2010Article
- Fhit regulates invasion of lung tumor cells.Oncogene · 2010Article
- Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women.Molecular and cellular biochemistry · 2010Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Alterations in the FHIT gene at 3p14.2 occur as early and frequent events in the development of several common human cancers. The ability of human Fhit-negative cells to form tumors in nude mice is suppressed by stable reexpression of Fhit protein. Fhit protein is a diadenosine P1,P3-triphosphate (ApppA) hydrolase whose fungal and animal homologs form a branch of the histidine triad (HIT) superfamily of nucleotide-binding proteins. Because the His-96 --> Asn substitution of Fhit, which retards ApppA hydrolase activity by seven orders of magnitude, did not block tumor-suppressor activity in vivo, we determined whether this mutation affected ApppA binding or particular steps in the ApppA catalytic cycle. Evidence is presented that His-96 --> Asn protein binds ApppA well and forms an enzyme-AMP intermediate extremely poorly, suggesting that Fhit-substrate complexes are the likely signaling form of the enzyme. The cocrystal structure of Fhit bound to Ado-p-CH2-p-ps-Ado (IB2), a nonhydrolyzable ApppA analog, was refined to 3.1 A, and the structure of His-96 --> Asn Fhit with IB2 was refined to 2.6 A, revealing that two ApppA molecules bind per Fhit dimer; identifying two additional adenosine-binding sites on the dimer surface; and illustrating that His-98 is positioned to donate a hydrogen bond to the scissile bridging oxygen of ApppA substrates. The form of Fhit bound to two ApppA substrates would present to the cell a dramatically phosphorylated surface, prominently displaying six phosphate groups and two adenosine moieties in place of a deep cavity lined with histidines, arginines, and glutamines.
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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.