Evidence map›Paper›PMID 23322302›Full record

ArticleGenes & development2013

Loss of RBF1 changes glutamine catabolism.

Brandon N Nicolay, Paulo A Gameiro, Katrin Tschöp, Michael Korenjak, Andreas M Heilmann, John M Asara, Gregory Stephanopoulos, Othon Iliopoulos, Nicholas J Dyson

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Review
  3. The significance ofFrontiers in immunology · 2024
    Review
  4. E2F regulation of theProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Relevance of pRB Loss in Human Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Metabolic Control by DNA Tumor Virus-Encoded Proteins.Pathogens (Basel, Switzerland) · 2021
    Review
  12. Article
  13. Review
  14. Article
  15. Methods and protocols · 2020
    Article
  16. Tumor Milieu Controlled by RB Tumor Suppressor.International journal of molecular sciences · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Brandon N NicolayLaboratory of Molecular Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA. bnicolay@partners.org
Paulo A Gameiro
Katrin Tschöp
Michael Korenjak
Andreas M Heilmann
John M Asara
Gregory Stephanopoulos
Othon Iliopoulos
Nicholas J Dyson
Harvard University · USMassachusetts General Hospital · USCenter for Cancer Research · USMassachusetts Institute of Technology · USMolecular Oncology (United States) · US

Funding

Drosophila Transgenic RNAi Resource ProjectR01GM084947 · NIGMS · HARVARD MEDICAL SCHOOL · PI PERRIMON, NORBERT · 2008 to 2019
$9.8M
Identification of Biomarkers for Early Detection of Renal Cell CarcinomaR01CA122591 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI ILIOPOULOS, OTHON · 2008 to 2012
$2.4M
Dissection and manipulation of RB functionR01CA163698 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DYSON, NICHOLAS J · 2012 to 2016
$1.8M
Hypoxia-induced Metabolic Changes in CancerR01CA160458 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI ILIOPOULOS, OTHON, STEPHANOPOULOS, GREGORY · 2012 to 2016
$1.6M
Understanding the role of SKP2 in small cell lung cancer progressionF32CA165856 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NICOLAY, BRANDON · 2012 to 2014
$149k
PROTON THERAPY RESEARCH AND TREATMENT CENTERC06CA059267 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI GOITEIN, MICHAEL · 1992 to 1995
–
NCI NIH HHS C06 CA059267NCI NIH HHS F32 CA165856NCI NIH HHS F32CA165856NCI NIH HHS R01 CA122591NCI NIH HHS R01 CA160458NCI NIH HHS R01 CA163698NIGMS NIH HHS R01 GM084947NIGMS NIH HHS R01-GM084947
6 · The paper itself

Abstract

Inactivation of the retinoblastoma tumor suppressor (pRB) alters the expression of a myriad of genes. To understand the altered cellular environment that these changes create, we took advantage of the Drosophila model system and used targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the metabolic changes that occur when RBF1, the fly ortholog of pRB, is removed. We show that RBF1-depleted tissues and larvae are sensitive to fasting. Depletion of RBF1 causes major changes in nucleotide synthesis and glutathione metabolism. Under fasting conditions, these changes interconnect, and the increased replication demand of RBF1-depleted larvae is associated with the depletion of glutathione pools. In vivo (13)C isotopic tracer analysis shows that RBF1-depleted larvae increase the flux of glutamine toward glutathione synthesis, presumably to minimize oxidative stress. Concordantly, H(2)O(2) preferentially promoted apoptosis in RBF1-depleted tissues, and the sensitivity of RBF1-depleted animals to fasting was specifically suppressed by either a glutamine supplement or the antioxidant N-acetyl-cysteine. Effects of pRB activation/inactivation on glutamine catabolism were also detected in human cell lines. These results show that the inactivation of RB proteins causes metabolic reprogramming and that these consequences of RBF/RB function are present in both flies and human cell lines.

Indexed as

AnimalsApoptosisCell Line, TumorDNA DamageDrosophila melanogasterDrosophila ProteinsFastingGlutamineGlutathioneHumansLarvaMutationNucleotidesOxidative StressRetinoblastoma ProteinStress, PhysiologicalDrosophila ProteinsGlutamineGlutathioneNucleotidesRbf protein, DrosophilaRetinoblastoma ProteinTranscription Factors

Identifiers

PMID23322302
PMCPMC3566311
OpenAlexW2165868533

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.