Evidence map›Paper›PMID 18552833›Full record

ArticleNature cell biology2008

Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis.

Nilkantha Sen, Makoto R Hara, Michael D Kornberg, Matthew B Cascio, Byoung-Il Bae, Neelam Shahani, Bobby Thomas, Ted M Dawson, Valina L Dawson, Solomon H Snyder and 1 more

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
12.7field-weighted citation impact, top 1% of its field
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

182 citing papers in PubMed, 1 synthesis or guideline pooled it, 400 citations in OpenAlex.

  1. Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Stress-induced nuclear GAPDH: Scientific update and clinical application.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. The Primary Cultivation of Oogonial Stem Cells from Black Rockfish (International journal of molecular sciences · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025
    Review
  19. Transferrin receptors.Experimental & molecular medicine · 2025
    Review
  20. S-Nitrosylation of CRTC1 in Alzheimer's disease impairs CREB-dependent gene expression induced by neuronal activity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article

122 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

11 authors at 3 institutions in 1 country.

Nilkantha SenSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Makoto R Hara
Michael D Kornberg
Matthew B Cascio
Byoung-Il Bae
Neelam Shahani
Bobby Thomas
Ted M Dawson
Valina L Dawson
Solomon H Snyder
Akira Sawa
Johns Hopkins Medicine · USJohns Hopkins University · USDuke University · US

Funding

UNDERSTANDING NO SIGNALING RESULTING IN NEUROPROTECTION.P50DA000266 · NIDA · JOHNS HOPKINS UNIVERSITY · PI WORLEY, PAUL F · 1985 to 2017
$45.2M
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
Nuclear pathway of DISC1 in major mental illnesses: biochemistry and cell biologyR01MH069853 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2004 to 2012
$3.2M
The Role of Parkin in Parkinson's DiseaseR01NS048206 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, TED M. · 2004 to 2009
$2.0M
NEUROTRANSMITTER RECEPTORSK05DA000074 · NIDA · JOHNS HOPKINS UNIVERSITY · PI SNYDER, SOLOMON H. · 1985 to 2009
$1.3M
COCAINE RECEPTOR--BIOCHEMICAL AND MOLECULAR STUDIESZ01DA000226 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI KUHAR, M J · 1993 to 1995
–
NIDA NIH HHS DA-00074NIDA NIH HHS DA-00226NIDA NIH HHS DA-00266NIDA NIH HHS K05 DA000074NIDA NIH HHS P50 DA000266NIMH NIH HHS MH-069853NIMH NIH HHS R01 MH069853NINDS NIH HHS NS-38377NINDS NIH HHS NS-48206NINDS NIH HHS P50 NS038377NINDS NIH HHS R01 NS048206
6 · The paper itself

Abstract

Besides its role in glycolysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) initiates a cell death cascade. Diverse apoptotic stimuli activate inducible nitric oxide synthase (iNOS) or neuronal NOS (nNOS), with the generated nitric oxide (NO) S-nitrosylating GAPDH, abolishing its catalytic activity and conferring on it the ability to bind to Siah1, an E3-ubiquitin-ligase with a nuclear localization signal (NLS). The GAPDH-Siah1 protein complex, in turn, translocates to the nucleus and mediates cell death; these processes are blocked by procedures that interfere with GAPDH-Siah1 binding. Nuclear events induced by GAPDH to kill cells have been obscure. Here we show that nuclear GAPDH is acetylated at Lys 160 by the acetyltransferase p300/CREB binding protein (CBP) through direct protein interaction, which in turn stimulates the acetylation and catalytic activity of p300/CBP. Consequently, downstream targets of p300/CBP, such as p53 (Refs 10,11,12,13,14,15), are activated and cause cell death. A dominant-negative mutant GAPDH with the substitution of Lys 160 to Arg (GAPDH-K160R) prevents activation of p300/CBP, blocks induction of apoptotic genes and decreases cell death. Our findings reveal a pathway in which NO-induced nuclear GAPDH mediates cell death through p300/CBP.

Indexed as

AcetylationAnimalsApoptosisCell LineCell NucleusEnzyme ActivationGlyceraldehyde-3-Phosphate DehydrogenasesHumansMacrophages, PeritonealMiceNitric OxideNitric Oxide Synthase Type IIp300-CBP Transcription FactorsTumor Suppressor Protein p53Glyceraldehyde-3-Phosphate DehydrogenasesNitric OxideNitric Oxide Synthase Type IIp300-CBP Transcription FactorsTumor Suppressor Protein p53

Identifiers

PMID18552833
PMCPMC2689382
OpenAlexW2066374288

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.