Evidence map›Paper›PMID 24652283›Full record

ArticleThe Journal of biological chemistry2014

Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation.

Sungki Hong, Bin Zhao, David B Lombard, Diane C Fingar, Ken Inoki

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Neuronal C/EBPβ Shortens the Lifespan via Inactivating NAMPT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Article
  4. Review
  5. Review
  6. Investigating the Regulation of Ribosomal Protein S6 Kinase 1 by CoAlation.International journal of molecular sciences · 2024
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Special issue on hypoxia.Experimental & molecular medicine · 2019
    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

5 authors at 2 institutions in 2 countries.

Sungki HongFrom the Life Sciences Institute.
Bin Zhao
David B Lombard
Diane C Fingar
Ken Inoki
University of Michigan–Ann Arbor · USZhejiang University · CN

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Role of TSC-mTORC1 pathway for podocyte injury in diabetic nephropathyR01DK083491 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI INOKI, KEN · 2009 to 2017
$3.0M
Regulation of one carbon metabolism and epigenetics by SIRT5R01GM101171 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOMBARD, DAVID BENNER · 2012 to 2021
$2.6M
Lysosomal cholesterol-dependent anabolic regulationR01DK124709 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI INOKI, KEN · 2022 to 2025
$2.1M
Mechanisms of tumor suppression by the chromatin deacetylase SIRT6R21CA177925 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOMBARD, DAVID BENNER · 2013 to 2014
$362k
NCI NIH HHS CA177925NCI NIH HHS R21 CA177925NIDDK NIH HHS DK083491NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK083491NIDDK NIH HHS R01 DK124709NIGMS NIH HHS GM101171NIGMS NIH HHS R01 GM101171
6 · The paper itself

Abstract

p70 ribosomal S6 kinase (S6K1), a major substrate of the mammalian target of rapamycin (mTOR) kinase, regulates diverse cellular processes including protein synthesis, cell growth, and survival. Although it is well known that the activity of S6K1 is tightly coupled to its phosphorylation status, the regulation of S6K1 activity by other post-translational modifications such as acetylation has not been well understood. Here we show that the acetylation of the C-terminal region (CTR) of S6K1 blocks mTORC1-dependent Thr-389 phosphorylation, an essential phosphorylation site for S6K1 activity. The acetylation of the CTR of S6K1 is inhibited by the class III histone deacetylases, SIRT1 and SIRT2. An S6K1 mutant lacking acetylation sites in its CTR shows enhanced Thr-389 phosphorylation and kinase activity, whereas the acetylation-mimetic S6K1 mutant exhibits decreased Thr-389 phosphorylation and kinase activity. Interestingly, relative to the acetylation-mimetic S6K1 mutant, the acetylation-defective mutant displays higher affinity toward Raptor, an essential scaffolding component of mTORC1 that recruits mTORC1 substrates. These observations indicate that sirtuin-mediated regulation of S6K1 acetylation is an additional important regulatory modification that impinges on the mechanisms underlying mTORC1-dependent S6K1 activation.

Indexed as

AcetylationAnimalsChlorocebus aethiopsCOS CellsEnzyme ActivationHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationPhosphorylationRibosomal Protein S6 Kinases, 70-kDaSignal TransductionSirtuin 1Sirtuin 2TOR Serine-Threonine KinasesMechanistic Target of Rapamycin Complex 1Multiprotein Complexesribosomal protein S6 kinase, 70kD, polypeptide 1Ribosomal Protein S6 Kinases, 70-kDaSIRT1 protein, humanSIRT2 protein, humanSirtuin 1Sirtuin 2TOR Serine-Threonine KinasesAcetylationmTORmTOR Complex (mTORC)PhosphorylationRapamycinS6 KinaseSirt1Sirtuins

Identifiers

PMID24652283
PMCPMC4036325
OpenAlexW1966411345

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.