ArticleCancer research2009
Depletion of guanine nucleotides leads to the Mdm2-dependent proteasomal degradation of nucleostemin.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- IMPDH Inhibition Decreases TERT Expression and Synergizes the Cytotoxic Effect of Chemotherapeutic Agents in Glioblastoma Cells.International journal of molecular sciences · 2024Article
- Autophagy mediates proteolysis of NPM1 and HEXIM1 and sensitivity to BET inhibition in AML cells.Oncotarget · 2016Article
- RRP12 is a crucial nucleolar protein that regulates p53 activity in osteosarcoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer.Oncotarget · 2015Article
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- FAK activity protects nucleostemin in facilitating breast cancer spheroid and tumor growth.Breast cancer research : BCR · 2015Article
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- Turning a new page on nucleostemin and self-renewal.Journal of cell science · 2014Article
- Nucleolar stress induces ubiquitination-independent proteasomal degradation of PICT1 protein.The Journal of biological chemistry · 2014Article
- Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer.Nature cell biology · 2013Article
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- Ubiquitin- and MDM2 E3 ligase-independent proteasomal turnover of nucleostemin in response to GTP depletion.The Journal of biological chemistry · 2012Article
- Cyclopentenyl cytosine induces senescence in breast cancer cells through the nucleolar stress response and activation of p53.Molecular pharmacology · 2011Article
- Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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- Reactive oxygen species regulate nucleostemin oligomerization and protein degradation.The Journal of biological chemistry · 2011Article
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- Nucleostemin: Another nucleolar "Twister" of the p53-MDM2 loop.Cell cycle (Georgetown, Tex.) · 2010Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Nucleostemin is a positive regulator of cell proliferation and is highly expressed in a variety of stem cells, tumors, and tumor cell lines. The protein shuttles between the nucleolus and the nucleus in a GTP-dependent fashion. Selective depletion of intracellular guanine nucleotides by AVN-944, an inhibitor of the de novo purine synthetic enzyme, IMP dehydrogenase, leads to the rapid disappearance of nucleostemin protein in tumor cell lines, an effect that does not occur with two other nucleolar proteins, nucleophosmin or nucleolin. Endogenous nucleostemin protein is completely stabilized by MG132, an inhibitor of the 26S proteasome, as are the levels of expressed enhanced green fluorescent protein-tagged nucleostemin, both wild-type protein and protein containing mutations at the G(1) GTP binding site. Nutlin-3a, a small molecule that disrupts the binding of the E3 ubiquitin ligase, Mdm2, to p53, stabilizes nucleostemin protein in the face of guanine nucleotide depletion, as does siRNA-mediated knockdown of Mdm2 expression and overexpression of a dominant-negative form of Mdm2. Neither Doxorubicin nor Actinomycin D, which cause the release of nucleostemin from the nucleolus, results in nucleostemin degradation. We conclude that nucleostemin is a target for Mdm2-mediated ubiquitination and degradation when not bound to GTP. Because this effect does not occur with other chemotherapeutic agents, the induction of nucleostemin protein degradation in tumor cells by IMP dehydrogenase inhibition or by other small molecules that disrupt GTP binding may offer a new approach to the treatment of certain neoplastic diseases.
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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.