Evidence map›Paper›PMID 20975832›Full record

ArticlePloS one2010

SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with p53.

Cian J Lynch, Zahid H Shah, Simon J Allison, Shafiq U Ahmed, Jack Ford, Lorna J Warnock, Han Li, Manuel Serrano, Jo Milner

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Splicing alterations in healthy aging and disease.Wiley interdisciplinary reviews. RNA · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Role of Sirtuins in Tumor Angiogenesis.Frontiers in oncology · 2019
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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 2 institutions in 2 countries.

Cian J LynchYCR p53 Research Unit, Department of Biology, University of York, York, United Kingdom. clynch@cnio.es
Zahid H Shah
Simon J Allison
Shafiq U Ahmed
Jack Ford
Lorna J Warnock
Han Li
Manuel Serrano
Jo Milner
University of York · GBSpanish National Cancer Research Centre · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe NAD-dependent deacetylase SIRT1 is a nutrient-sensitive coordinator of stress-tolerance, multiple homeostatic processes and healthspan, while p53 is a stress-responsive transcription factor and our paramount tumour suppressor. Thus, SIRT1-mediated inhibition of p53 has been identified as a key node in the common biology of cancer, metabolism, development and ageing. However, precisely how SIRT1 integrates such diverse processes remains to be elucidated. METHODOLOGY/PRINCIPAL

findingsHere we report that SIRT1 is alternatively spliced in mammals, generating a novel SIRT1 isoform: SIRT1-ΔExon8. We show that SIRT1-ΔExon8 is expressed widely throughout normal human and mouse tissues, suggesting evolutionary conservation and critical function. Further studies demonstrate that the SIRT1-ΔExon8 isoform retains minimal deacetylase activity and exhibits distinct stress sensitivity, RNA/protein stability, and protein-protein interactions compared to classical SIRT1-Full-Length (SIRT1-FL). We also identify an auto-regulatory loop whereby SIRT1-ΔExon8 can regulate p53, while in reciprocal p53 can influence SIRT1 splice variation. CONCLUSIONS/SIGNIFICANCE: We characterize the first alternative isoform of SIRT1 and demonstrate its evolutionary conservation in mammalian tissues. The results also reveal a new level of inter-dependency between p53 and SIRT1, two master regulators of multiple phenomena. Thus, previously-attributed SIRT1 functions may in fact be distributed between SIRT1 isoforms, with important implications for SIRT1 functional studies and the current search for SIRT1-activating therapeutics to combat age-related decline.

Indexed as

Alternative SplicingAcetylationAnimalsExonsHumansMiceReverse Transcriptase Polymerase Chain ReactionSirtuin 1Tumor Suppressor Protein p53SIRT1 protein, humanSirt1 protein, mouseSirtuin 1Tumor Suppressor Protein p53

Identifiers

PMID20975832
PMCPMC2958826
OpenAlexW2047231656

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.