ArticleLeukemia research2008
Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption.
Article in Leukemia research, 2008. 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, 56 citations in OpenAlex.
- Expression of IMPDH mRNA after mycophenolate administration in male volunteers.BioMed research international · 2014Trial
- ExploringAntimicrobial agents and chemotherapy · 2026Article
- AVN944 Elicits Apoptotic Responses and Impedes Tumorigenic Potential in Ewing's Sarcoma Cells.International journal of biological sciences · 2026Article
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Impaired inosine monophosphate dehydrogenase leads to plant-specific ribosomal stress responses in Arabidopsis thaliana.Journal of plant research · 2024Article
- rDNA Transcription in Developmental Diseases and Stem Cells.Stem cell reviews and reports · 2023Review
- Nucleolar stress: Molecular mechanisms and related human diseases.Cancer science · 2023Review
- Compartmentalization and regulation of GTP in control of cellular phenotypes.Trends in molecular medicine · 2022Review
- Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid.Journal of biomedical science · 2021Article
- Nucleotide depletion reveals the impaired ribosome biogenesis checkpoint as a barrier against DNA damage.The EMBO journal · 2020Article
- Review
- IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma.Nature cell biology · 2019Article
- Genome-wide identification and characterization of the RIO atypical kinase family in plants.Genes & genomics · 2018Article
- Article
- The Evolution of the Ribosomal Protein-MDM2-p53 Pathway.Cold Spring Harbor perspectives in medicine · 2016Review
- Functional characterization of the ribosome biogenesis factors PES, BOP1, and WDR12 (PeBoW), and mechanisms of defective cell growth and proliferation caused by PeBoW deficiency in Arabidopsis.Journal of experimental botany · 2016Article
- In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes.PloS one · 2016Article
- The nucleolar GTPase nucleostemin-like 1 plays a role in plant growth and senescence by modulating ribosome biogenesis.Journal of experimental botany · 2015Article
- Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer.Oncotarget · 2015Article
- Cytochrome C and Caspase-3/7 are Involved in Mycophenolic Acid- Induced Apoptosis in Genetically Engineered PC12 Neuronal Cells Expressing the p53 gene.Iranian journal of pharmaceutical research : IJPR · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Inosine monophosphate dehydrogenase (IMPDH) is a pivotal enzyme in the de novo pathway of guanine nucleotide biosynthesis. Inhibitors of this enzyme decrease intracellular guanine nucleotide levels by 50-80% and have potential as anti-neoplastic agents. Both mycophenolic acid (MPA) and AVN-944 are highly specific inhibitors of IMPDH that cause cell cycle arrest or apoptosis in lymphocytes and leukemic cell lines. We have examined the mechanisms by which these two agents cause cytotoxicity. Both MPA and AVN-944 inhibit the growth of K562 cells, and induce apoptosis in Raji B and CCRF-CEM T cells. Both compounds strikingly inhibit RNA synthesis within 2 h of exposure. Depletion of guanine nucleotides by MPA and AVN-944 also causes an early and near-complete reduction in levels of the 45S precursor rRNA synthesis and the concomitant translocation of nucleolar proteins including nucleolin, nucleophosmin, and nucleostemin from the nucleolus to the nucleoplasm. This efflux correlates temporally with the sustained induction of p53 in cell lines with wild-type p53. We conclude that inhibition of IMPDH causes a primary reduction in rRNA synthesis and secondary nucleolar disruption and efflux of nucleolar proteins that most likely mediate cell cycle arrest or apoptosis. The ability of AVN-944 to induce apoptosis in a number of leukemic cell lines supports its potential utility in the treatment of hematologic malignancies.
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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.