Evidence map›Paper›PMID 22740686›Full record

ArticleScience signaling2012

Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation.

Nikolaos Patsoukis, Julia Brown, Victoria Petkova, Fang Liu, Lequn Li, Vassiliki A Boussiotis

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 332 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
332citing papers in PubMed, 3 pooled it
8.8field-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

332 citing papers in PubMed, 3 syntheses or guidelines pooled it, 511 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
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  7. Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
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  14. Memory-like CD8Frontiers in immunology · 2026
    Article
  15. Review
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  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Nikolaos PatsoukisDepartment of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Julia Brown
Victoria Petkova
Fang Liu
Lequn Li
Vassiliki A Boussiotis
Harvard University · USBeth Israel Deaconess Medical Center · US

Funding

Prevention of acute GvHD by inhibition of cdk2R21HL107997 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BOUSSIOTIS, VASSILIKI A · 2011 to 2012
$482k
The role of Rap1 and its novel associated molecules in T cell responsesR56AI043552 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BOUSSIOTIS, VASSILIKI A · 2011 to 2011
$392k
NHLBI NIH HHS HL107997-01NHLBI NIH HHS R21 HL107997NIAID NIH HHS R56 AI043552NIAID NIH HHS R56AI43552
6 · The paper itself

Abstract

The receptor programmed death 1 (PD-1) inhibits T cell proliferation and plays a critical role in suppressing self-reactive T cells, and it also compromises antiviral and antitumor responses. To determine how PD-1 signaling inhibits T cell proliferation, we used human CD4(+) T cells to examine the effects of PD-1 signaling on the molecular control of the cell cycle. The ubiquitin ligase SCF(Skp2) degrades p27(kip1), an inhibitor of cyclin-dependent kinases (Cdks), and PD-1 blocked cell cycle progression through the G(1) phase by suppressing transcription of SKP2, which encodes a component of this ubiquitin ligase. Thus, in T cells stimulated through PD-1, Cdks were not activated, and two critical Cdk substrates were not phosphorylated. Activation of PD-1 inhibited phosphorylation of the retinoblastoma gene product, which suppressed expression of E2F target genes. PD-1 also inhibited phosphorylation of the transcription factor Smad3, which increased its activity. These events induced additional inhibitory checkpoints in the cell cycle by increasing the abundance of the G(1) phase inhibitor p15(INK4) and repressing the Cdk-activating phosphatase Cdc25A. PD-1 suppressed SKP2 transcription by inhibiting phosphoinositide 3-kinase-Akt and Ras-mitogen-activated and extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling. Exposure of cells to the proliferation-promoting cytokine interleukin-2 restored activation of MEK-ERK signaling, but not Akt signaling, and only partially restored SKP2 expression. Thus, PD-1 blocks cell cycle progression and proliferation of T lymphocytes by affecting multiple regulators of the cell cycle.

Indexed as

CD4-Positive T-Lymphocytescdc25 PhosphatasesCell Cycle CheckpointsCyclin-Dependent Kinase Inhibitor p16G1 PhaseHumansInterleukin-2MAP Kinase Signaling SystemPhosphorylationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-aktras ProteinsRetinoblastoma ProteinSmad3 ProteinS-Phase Kinase-Associated ProteinsTranscription, GeneticCDC25A protein, humancdc25 PhosphatasesCyclin-Dependent Kinase Inhibitor p16IL2 protein, humanInterleukin-2PDCD1 protein, humanProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-aktras ProteinsRetinoblastoma ProteinSmad3 ProteinSMAD3 protein, humanS-Phase Kinase-Associated Proteins

Identifiers

PMID22740686
PMCPMC5498435
OpenAlexW2144256523

What OpenQuestion holds

Textmetadata
LicenceTDM
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.