Affinage

PDCD4

Programmed cell death protein 4 · UniProt Q53EL6

Length
469 aa
Mass
51.7 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDCD4 is a tumor suppressor that restrains cap-dependent translation initiation and inflammatory and oncogenic signaling, with loss-of-function promoting neoplastic transformation (PMID:10570194, PMID:18296647). Mechanistically, PDCD4 binds the 40S small ribosomal subunit through its C-terminal domain contacting eIF4A at the mRNA entry site while its N-terminal domain inserts into the mRNA channel and decoding site, blocking the eIF4F-independent role of eIF4A during 5' UTR scanning (PMID:39117603). Through eIF4A engagement it selectively suppresses translation of mRNAs bearing structured 5' UTRs, including p53 and Sin1/MAPKAP1, the latter linking PDCD4 to mTORC2 activity, Snail expression, and cancer cell invasion (PMID:22033922, PMID:28692058). PDCD4 abundance is controlled by mitogenic signaling: S6K1 and Akt phosphorylate it at Ser67 (and Ser457), creating a phosphodegron that recruits SCF(βTrCP) for polyubiquitylation and proteasomal degradation, a step potentiated by MEK-ERK signaling (PMID:17053147, PMID:16357133, PMID:18296647); additional E3 ligase adaptors SKP2, DTL (CUL4-DDB1), and CRL3(IBTK) likewise target PDCD4 for turnover (PMID:30760284, PMID:31409387, PMID:25882842). Independent of translation, PDCD4 suppresses AP-1 transcription by binding c-Jun directly to block JNK-mediated phosphorylation and p300 coactivator recruitment (PMID:15334056), and it inhibits autophagy through its MA-3 domains by suppressing ATG5 expression and ATG12-ATG5 complex formation (PMID:23486359). In vivo, PDCD4 modulates inflammatory and metabolic disease via IL-6/STAT3 signaling in colitis-associated cancer and Daxx/PPARγ/IL-10 signaling in microglia (PMID:26891257, PMID:38822367).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 Medium

    Established PDCD4 as a functional suppressor of neoplastic transformation, defining the gene's tumor-suppressor identity before its molecular mechanism was known.

    Evidence Antisense knockdown converting transformation-resistant cells to sensitive, reversed by sense rescue, in a defined cell system

    PMID:10570194

    Open questions at the time
    • No molecular mechanism of suppression identified
    • Effect shown in one engineered cell variant system
  2. 2001 Low

    Identified PDCD4 as a direct transcriptional target of an oncogene, placing it downstream of oncogenic transcription programs.

    Evidence Differential display in v-Myb-inducible avian myelomonocytic cells

    PMID:11313950

    Open questions at the time
    • Limited mechanistic follow-up at the protein level
    • Avian system; human relevance not established here
  3. 2002 Medium

    First connected PDCD4 to the translation apparatus, showing physical association with ribosomal and initiation components.

    Evidence Yeast two-hybrid and GST pulldown with RPS13 and eIF4G, polysome sedimentation in senescent fibroblasts

    PMID:12054647

    Open questions at the time
    • Functional consequence of eIF4G binding not resolved
    • Did not establish eIF4A as the key target
  4. 2005 Medium

    Defined Akt as an upstream kinase regulating PDCD4 localization and AP-1 suppression, linking PI3K-Akt signaling to PDCD4 inactivation.

    Evidence In vitro and in vivo kinase assays at Ser67/Ser457, subcellular imaging, AP-1 luciferase reporter

    PMID:16357133

    Open questions at the time
    • Did not identify the degradation machinery downstream of phosphorylation
    • Single lab
  5. 2006 High

    Resolved the degradation mechanism: S6K1-mediated Ser67 phosphorylation triggers SCF(βTrCP)-dependent ubiquitylation and turnover, coupling mitogen signaling to relief of translational repression.

    Evidence In vivo phosphorylation, Co-IP, ubiquitylation assay, phospho-resistant mutant with translation reporter and cell-size/cycle readouts

    PMID:17053147

    Open questions at the time
    • Identity of the structured-UTR mRNA targets not fully enumerated
    • Did not address additional E3 ligases
  6. 2008 High

    Confirmed PDCD4 as a haploinsufficient tumor suppressor in vivo and integrated MEK-ERK with the Akt/S6K1-βTrCP degradation axis under tumor-promoter stimulation.

    Evidence Pdcd4-haploinsufficient mice, Co-IP, ubiquitylation, proteasome inhibition under TPA treatment

    PMID:18296647

    Open questions at the time
    • Precise division of labor between Akt and p70S6K phosphosites not fully dissected
  7. 2008 Medium

    Showed PDCD4 interferes with p53-mediated transactivation, expanding its role to p53 pathway and DNA-damage survival responses.

    Evidence Stable shRNA knockdown, p53-responsive reporter assays, UV survival/apoptosis readouts

    PMID:18427550

    Open questions at the time
    • Mechanistic basis of interference (transcriptional vs translational) not separated here
    • Single cell line
  8. 2011 High

    Demonstrated that PDCD4 represses p53 mRNA translation via eIF4A and the p53 5' UTR stem-loop, providing a specific mRNA target of its translational control.

    Evidence RNA-IP, 5' UTR-luciferase reporter, eIF4A-binding mutant, DNA-damage de-repression

    PMID:22033922

    Open questions at the time
    • Genome-wide scope of structured-UTR targets not defined
    • Single lab
  9. 2012 Medium

    Placed PDCD4 phosphorylation within mTORC1 control of global protein synthesis, parallel to the 4E-BP/eIF4E axis.

    Evidence Genetic/pharmacological mTORC1 and p70S6K1 manipulation, 35S-methionine incorporation in 4E-BP1/2 DKO MEFs and rat liver

    PMID:23105104

    Open questions at the time
    • Relative contribution of PDCD4 vs eIF4B to the effect not isolated
  10. 2012 Medium

    Mapped a transcriptional arm of PDCD4 tumor suppression, showing its loss activates JNK/AP-1 via β-catenin/c-Myc-driven MAP4K1 induction.

    Evidence siRNA knockdown, ChIP at the MAP4K1 promoter, promoter mutation, DN-Tcf4 epistasis, AP-1 reporter

    PMID:22801218

    Open questions at the time
    • Connection to PDCD4's translational activity not established
  11. 2013 Medium

    Identified autophagy regulation as a distinct PDCD4 function, suppressing ATG5 and ATG12-ATG5 complex formation via its MA-3 domains.

    Evidence Overexpression/knockdown, LC3/p62 flux assays, ATG5 expression, domain mutants, xenograft

    PMID:23486359

    Open questions at the time
    • Whether ATG5 suppression is translational or transcriptional not resolved
    • Single lab
  12. 2015 Medium

    Added CRL3(IBTK) as an E3 ligase controlling PDCD4 turnover, broadening the degradation network beyond SCF(βTrCP).

    Evidence Co-IP, ubiquitylation assay, RNAi, Bcl-xL 5' UTR translation reporter

    PMID:25882842

    Open questions at the time
    • Phosphodependence of IBTK recognition not defined
    • Single lab
  13. 2016 Medium

    Revealed in vivo inflammatory and metabolic roles for PDCD4 through IL-6/STAT3 in colitis-associated cancer and macrophage lipoautophagy in atherosclerosis.

    Evidence Pdcd4 KO mice in DSS/AOM colitis-CRC and ApoE-KO/HFD atherosclerosis models, bone marrow transplant, pathway blockade (sgp130Fc)

    PMID:26775706 PMID:26891257

    Open questions at the time
    • Direct molecular target of PDCD4 in these pathways not pinpointed
    • Tissue/cell-type-specific mechanisms partly inferred
  14. 2016 Medium

    Showed PDCD4 protein levels are set post-transcriptionally by trans-acting RNA factors, with SRSF3 repressing PDCD4 splicing, export, and translation.

    Evidence SRSF3 knockdown, isoform RT-PCR, nuclear/cytoplasmic fractionation, translation assay in colon cancer cells

    PMID:26773498

    Open questions at the time
    • Direct SRSF3 binding sites on pdcd4 mRNA not mapped
  15. 2017 High

    Connected PDCD4's eIF4A-dependent translational repression to mTORC2 by identifying Sin1/MAPKAP1 mRNA as a structured-UTR target controlling invasion.

    Evidence 5' UTR reporter, eIF4A-binding mutant (D253A,D418A), polysome profiling, KO rescue, silvestrol

    PMID:28692058

    Open questions at the time
    • Generality across tumor types not established
  16. 2017 Medium

    Established oncogenic kinase control of PDCD4 via the STAT5-miR-21 axis in leukemia, explaining PDCD4 loss downstream of BCR-ABL1 and FLT3-ITD.

    Evidence miRNA microarray, STAT binding site analysis on miR-21 promoter, proteomics, kinase inhibitor experiments, primary CD34+ cells

    PMID:29100302

    Open questions at the time
    • Direct miR-21 binding on PDCD4 mRNA not shown in this study
  17. 2019 Medium

    Expanded the E3 ligase repertoire degrading PDCD4 to SKP2 and DTL, linking PDCD4 turnover to proliferation and radiation resistance.

    Evidence AP-MS, reciprocal Co-IP, ubiquitination assays, overexpression/knockdown, in vitro and in vivo tumor models

    PMID:30760284 PMID:31409387

    Open questions at the time
    • Hierarchy and redundancy among βTrCP, SKP2, DTL, IBTK ligases not resolved
  18. 2020 Medium

    Showed PDCD4 stability is a node controlling chemotherapy response, with mTORC1 inactivation during mitotic arrest stabilizing PDCD4 to inhibit eIF4A and promote death.

    Evidence Non-phosphorylatable raptor mutant, mTORC1 activity assays, Taxol cytotoxicity, eIF4A inhibitors during mitotic arrest

    PMID:33027666

    Open questions at the time
    • Specific PDCD4-controlled mRNAs driving death not identified
  19. 2020 Medium

    Identified RNA-binding proteins La and HuR as positive regulators of PDCD4 by counteracting miR-21 repression at the 3' UTR.

    Evidence RNA-IP, translation reporter, fractionation, La/HuR co-transfection, proliferation/apoptosis assays under LPS

    PMID:33288677

    Open questions at the time
    • Interplay with the STAT5-miR-21 leukemia axis not integrated
  20. 2020 Medium

    Extended PDCD4 function to metabolism and additional signaling outputs, including PPARα-dependent β-oxidation and Keap1/Nrf2 and EIF3H/c-Jun control.

    Evidence Pdcd4 KO/overexpression with PPARα rescue (hepatocytes), overexpression with Co-IP/MS for EIF3H and Keap1 readouts, xenografts

    PMID:32064160 PMID:32195018 PMID:35051553

    Open questions at the time
    • Direct molecular link between PDCD4 and PPARα/Keap1 not demonstrated
    • Keap1 finding is overexpression-based and low confidence
  21. 2021 Medium

    Defined a microglia-specific neuroinflammatory mechanism in which PDCD4 suppresses Daxx-mediated PPARγ nuclear translocation and IL-10, linking it to depressive-like behavior.

    Evidence Microglial conditional Pdcd4 KO, LPS model, PPARγ translocation and IL-10 readouts, IL-10Rα neutralization rescue

    PMID:38822367

    Open questions at the time
    • Direct PDCD4-Daxx interaction not biochemically resolved
  22. 2024 High

    Provided the structural basis for translational repression, showing PDCD4 bridges eIF4A and the 40S mRNA channel to block eIF4F-independent eIF4A scanning function.

    Evidence Cryo-EM of multiple PDCD4-40S-initiation factor complexes, quantitative binding, in vitro translation

    PMID:39117603

    Open questions at the time
    • How phosphorylation alters ribosome binding not structurally captured
    • Selectivity for specific structured 5' UTRs not structurally explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse degradation, RNA-regulatory, and signaling inputs are integrated to set PDCD4 levels and select among its translational versus transcriptional and metabolic outputs in a given cell context remains unresolved.
  • No unified hierarchy of the βTrCP/SKP2/DTL/IBTK ligases established
  • Genome-wide map of PDCD4-repressed structured-UTR mRNAs lacking
  • Context determinants of translational vs transcriptional roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0045182 translation regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005840 ribosome 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2
Partners
BTRCDTLEIF4AEIF4G1IBTKJUNRPS13SKP2
Complex memberships
PDCD4-40S ribosomal subunit complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 Cryo-EM structures of human PDCD4 bound to the 40S small ribosomal subunit (in Pdcd4-40S, Pdcd4-40S-eIF4A-eIF3-eIF1 complexes) reveal that the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) inserts into the mRNA channel and decoding site. Quantitative binding and in vitro translation assays confirmed the NTD is critical for ribosomal recruitment and that PDCD4 blocks the eIF4F-independent role of eIF4A during 5' UTR scanning. Single-particle cryo-EM, quantitative binding assays, in vitro translation assays Nature Communications High 39117603
2006 In response to mitogens, PDCD4 is phosphorylated on Ser67 by S6K1 and subsequently ubiquitylated and degraded via the SCF(βTrCP) E3 ubiquitin ligase. Expression of a stable PDCD4 mutant unable to bind βTrCP inhibited translation of an mRNA with a structured 5' UTR, reduced cell size, and slowed cell cycle progression. In vivo phosphorylation assay, co-immunoprecipitation, ubiquitylation assay, stable cell line expression of phosphorylation-resistant mutant, translation reporter assay Science High 17053147
2005 Akt phosphorylates PDCD4 at Ser67 and Ser457 in vitro and in vivo. Phosphorylation by Akt causes nuclear translocation of PDCD4 and significantly decreases the ability of PDCD4 to suppress AP-1-responsive promoter transactivation by c-Jun. In vitro kinase assay, in vivo phosphorylation (cell-based), luciferase reporter assay, subcellular localization imaging Cancer Research Medium 16357133
2008 Tumor promoter TPA decreases PDCD4 protein levels via proteasomal degradation mediated by PKC-dependent PI3K-Akt-mTOR-p70S6K and MEK-ERK signaling. Both Akt and p70S6K phosphorylate PDCD4, enabling binding of the E3 ubiquitin ligase βTrCP and ubiquitylation; MEK-ERK facilitates subsequent proteasomal degradation. Pdcd4-haploinsufficient mice show increased tumor formation, establishing Pdcd4 as a haploinsufficient tumor suppressor. In vivo phosphorylation, co-immunoprecipitation, ubiquitylation assay, proteasome inhibitor treatment, Pdcd4-deficient mouse model Cancer Research High 18296647
2004 PDCD4 interferes with JNK-mediated phosphorylation of c-Jun by interacting with c-Jun directly, blocking JNK access without globally suppressing JNK activity. Additionally, PDCD4 blocks recruitment of the coactivator p300 by c-Jun, thereby suppressing AP-1-dependent transcription. Co-immunoprecipitation, in vitro kinase assay, reporter gene assay Oncogene Medium 15334056
2011 PDCD4 suppresses translation of p53 mRNA via its eIF4A-interacting activity and the structured 5' UTR of p53 mRNA. PDCD4 was shown to associate with p53 mRNA, inhibit its translation in a manner dependent on eIF4A interaction and the p53 5' UTR stem-loop, and DNA-damaging agents decrease PDCD4 levels, thereby de-repressing p53 translation. RNA immunoprecipitation, translation reporter assay (5' UTR-luciferase), eIF4A-binding mutant analysis, western blot Journal of Biological Chemistry High 22033922
2012 p70S6K1 phosphorylates PDCD4, and this phosphorylation (together with eIF4B phosphorylation) is required to sustain global protein synthesis rates downstream of mTORC1, in addition to the 4E-BP/eIF4E axis. Genetic/pharmacological inhibition of mTORC1 and p70S6K1, protein synthesis measurement (35S-methionine incorporation), cell-based assays in 4E-BP1/2 double-knockout MEFs and fasted rat liver Journal of Biological Chemistry Medium 23105104
2017 PDCD4 inhibits translation of Sin1 (MAPKAP1) mRNA via its eIF4A-binding MA-3 domains in a 5' UTR-dependent manner, thereby suppressing mTORC2 kinase activity and reducing Snail expression and colon cancer cell invasion. The eIF4A-binding mutant Pdcd4(D253A,D418A) failed to inhibit Sin1 translation or invasion. 5' UTR-luciferase reporter assay, eIF4A-binding mutant analysis, polysome profiling, Pdcd4 KO cell lines, invasion assay, eIF4A inhibitor (silvestrol) Oncogene High 28692058
2002 PDCD4 interacts with ribosomal protein S13 (RPS13) in in vitro binding assays, co-localizes with polysome fractions, and interacts with eIF4G (by GST pulldown) but not eIF4E, suggesting PDCD4 modulates eIF4G-dependent translation in senescent fibroblasts. Yeast two-hybrid, in vitro binding assay (GST pulldown), sucrose gradient fractionation (polysome sedimentation) Biochemical and Biophysical Research Communications Medium 12054647
2019 SKP2 promotes PDCD4 phosphorylation, ubiquitination, and proteasomal degradation. Reciprocal Co-IP and mass spectrometry confirmed direct interaction between SKP2 and PDCD4. SKP2 promotes breast cancer cell proliferation and radiation resistance through PDCD4 suppression. Affinity-purification mass spectrometry, reciprocal Co-IP, ubiquitination assay, SKP2 stable overexpression/knockdown, in vitro and in vivo tumor models Journal of Experimental & Clinical Cancer Research Medium 30760284
2019 DTL (a CUL4-DDB1 associated factor) interacts with PDCD4 and promotes its ubiquitin-dependent proteasomal degradation. Co-IP, immunofluorescence co-localization, and in vitro ubiquitination assays confirmed DTL as a novel E3 ligase substrate adaptor for PDCD4. Affinity-purification mass spectrometry, Co-IP, immunofluorescence, in vitro ubiquitination assay, functional proliferation/invasion assays Journal of Experimental & Clinical Cancer Research Medium 31409387
2015 IBtkα forms a CRL3(IBTK) complex and ubiquitylates PDCD4 for proteasomal degradation. IBtkα was identified as a PDCD4 interactor; serum-induced PDCD4 degradation required both IBtkα and Cul3. IBtkα depletion caused PDCD4 accumulation and decreased translation of Bcl-xL mRNA. Co-immunoprecipitation, ubiquitylation assay, RNAi knockdown, luciferase translation reporter assay Journal of Biological Chemistry Medium 25882842
2008 Pdcd4 knockdown in HeLa cells by stable shRNA leads to increased expression of p21(Waf1/Cip1) and other p53-regulated genes. Reporter gene studies show Pdcd4 interferes with p53-mediated transactivation. Knockdown cells show decreased apoptosis and increased survival after UV irradiation. Stable shRNA knockdown, reporter gene assay (p53-responsive promoters), UV irradiation survival assay, western blot Oncogene Medium 18427550
2013 PDCD4 inhibits autophagy in multiple cell types in vitro and in vivo by suppressing the expression of ATG5 and the formation of the ATG12-ATG5 complex. The MA-3 domains of PDCD4 are required for this inhibitory activity. PDCD4 overexpression/knockdown, autophagy flux assays (LC3 conversion, p62), ATG5 expression analysis, domain mutant analysis, in vivo xenograft Autophagy Medium 23486359
2012 Pdcd4 knockdown increases MAP4K1 expression and phospho-c-Jun levels via a β-catenin/Tcf4-dependent upregulation of c-Myc, which directly binds the MAP4K1 promoter at -536 bp (confirmed by ChIP), thereby activating JNK/AP-1 signaling and tumor cell invasion. siRNA knockdown, ChIP assay, promoter mutation analysis, dominant-negative Tcf4 overexpression, AP-1 reporter assay Biochimica et Biophysica Acta Medium 22801218
2016 SRSF3 represses PDCD4 protein expression through two coordinated mechanisms: (1) repressing alternative splicing and nuclear export of minor pdcd4 mRNA isoforms, and (2) repressing translation of the major pdcd4 mRNA isoform. Knockdown of SRSF3 increased PDCD4 protein levels in SW480 colon cancer cells. SRSF3 knockdown, mRNA isoform analysis (RT-PCR), nuclear/cytoplasmic fractionation, translation assay Biochemical and Biophysical Research Communications Medium 26773498
2020 PDCD4 promotes hepatocellular lipid accumulation by negatively regulating PPARα expression and PPARα-dependent peroxisomal β-oxidation genes (Acox1-3). Pdcd4 knockout suppressed FFA-induced lipid accumulation; rescue experiments confirmed the PPARα pathway is required. Pdcd4 knockout (lentivirus), Pdcd4 overexpression, lipid accumulation assay, gene expression analysis (RT-PCR and western blot), PPARα knockdown rescue experiment Molecular and Cellular Endocrinology Medium 35051553
2020 The RNA-binding proteins La and HuR cooperatively bind the 3' UTR of PDCD4 mRNA and counteract miR-21-mediated translation repression. LPS causes nuclear-cytoplasmic translocation of HuR and increases cellular La expression; their cooperative binding enhances PDCD4 expression, reduces proliferation, and promotes apoptosis. RNA immunoprecipitation, translation reporter assay, nuclear-cytoplasmic fractionation, co-transfection of La and HuR, cell proliferation and apoptosis assays Journal of Biological Chemistry Medium 33288677
2020 During mitotic arrest, mTORC1 activity is dramatically reduced (due to raptor phosphorylation), leading to PDCD4 stabilization and consequent inhibition of eIF4A, which promotes cell death. A non-phosphorylatable raptor mutant reactivates mTORC1, degrades PDCD4, and reduces Taxol cytotoxicity; pharmacological eIF4A inhibition rescues Taxol sensitivity in resistant cells. Non-phosphorylatable raptor mutant expression, mTORC1 activity assay, Taxol cytotoxicity assay, eIF4A inhibitor (silvestrol/rocaglamide), PDCD4 western blot during mitotic arrest Cell Reports Medium 33027666
2016 Pdcd4 deficiency in macrophages enhanced lipoautophagy (autophagy-mediated lipid degradation), prevented foam cell formation in vitro, and reduced atherosclerotic lesions in high-fat-fed ApoE-KO mice. Bone marrow transplantation confirmed that PDCD4-mediated autophagy in hematopoietic cells drives atherosclerosis. Pdcd4 knockout mouse, bone marrow transplantation, autophagy flux assay, foam cell formation assay, in vivo atherosclerosis model (ApoE-KO + HFD) Cell Death & Disease Medium 26775706
2016 Pdcd4 deficiency accelerated colitis and colitis-associated colorectal cancer in mice via upregulation of IL-6 and enhanced activation of the STAT3 signaling pathway. Blockade of IL-6/STAT3 with sgp130Fc reversed the pro-proliferative effect of Pdcd4 deficiency in vivo. Pdcd4 knockout mouse (DSS/AOM colitis-CRC model), cytokine ELISA, western blot, BrdU incorporation, sgp130Fc treatment Inflammatory Bowel Diseases Medium 26891257
2021 Microglial Pdcd4 promotes neuroinflammatory responses by inhibiting Daxx-mediated PPARγ nuclear translocation, thereby suppressing anti-inflammatory IL-10 expression. Microglial conditional Pdcd4 knockout protected against LPS-induced microglial hyperactivation and depressive-like behavior; this protection was abolished by intracerebroventricular IL-10Rα neutralizing antibody. Microglial conditional Pdcd4 knockout mouse, LPS neuroinflammation model, PPARγ nuclear translocation assay, IL-10 ELISA, behavioral assays, neutralizing antibody injection Journal of Neuroinflammation Medium 38822367
2017 BCR-ABL1 in CML activates STAT5, which binds the miR-21 promoter and drives miR-21 expression; miR-21 in turn suppresses PDCD4 protein. This phosphoSTAT5-miR-21-PDCD4 axis also operates in AML cells driven by FLT3-ITD. PDCD4 was identified as a STAT5/miR-21 target by proteomics. miRNA microarray, miR-21 promoter STAT binding site analysis, proteomic identification of PDCD4, BCR-ABL1 and FLT3-ITD inhibitor experiments, CML primary CD34+ cell validation Oncotarget Medium 29100302
2001 The chicken Pdcd4 gene is a direct transcriptional target of the v-Myb oncogene, identified by differential display in v-Myb-inducible myelomonocytic cells. This represents the first evidence of direct transcriptional regulation of Pdcd4 by an oncogene. Differential display, v-Myb inducible cell system, promoter/transcriptional analysis Oncogene Low 11313950
1999 PDCD4 (H731) protein inhibits tumor promoter-induced neoplastic transformation. Antisense-mediated reduction of Pdcd4 in transformation-resistant P- cells converted them to a transformation-sensitive phenotype; this was reversed by re-expression of Pdcd4 sense sequence. Stable antisense transfection, anchorage-independent colony formation assay, sense rescue experiment PNAS Medium 10570194
2020 PDCD4 overexpression in lung cancer cells increased Keap1 expression, which suppressed the p62-Nrf2 pathway. PDCD4-overexpressing cells showed increased apoptosis, inhibited proliferation, and reduced EMT markers. This was confirmed in xenograft models. Stable PDCD4 overexpression, western blot, apoptosis assay, xenograft tumor model American Journal of Cancer Research Low 32195018
2020 EIF3H interacts with PDCD4 (confirmed by Co-IP and immunofluorescent co-localization). PDCD4 overexpression reduces EIF3H mRNA and protein levels by suppressing c-Jun-induced EIF3H transcription. EIF3H promotes EMT and LUAD cell metastasis, which is abrogated by PDCD4. Co-immunoprecipitation combined with mass spectrometry, immunofluorescent co-localization, PDCD4 overexpression, western blot, migration/invasion assays, xenograft model American Journal of Cancer Research Medium 32064160

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science (New York, N.Y.) 610 17053147
2011 Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. Science signaling 293 22087031
2009 The tumour suppressor Pdcd4: recent advances in the elucidation of function and regulation. Biology of the cell 266 19356152
1999 Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proceedings of the National Academy of Sciences of the United States of America 235 10570194
2005 Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer research 134 16357133
2008 Translation inhibitor Pdcd4 is targeted for degradation during tumor promotion. Cancer research 133 18296647
2019 Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions. International journal of molecular sciences 125 31075975
2004 Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun. Oncogene 117 15334056
2012 Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis. The Journal of biological chemistry 113 23105104
2018 The role of Pdcd4 in tumour suppression and protein translation. Biology of the cell 103 29806708
2019 SKP2 promotes breast cancer tumorigenesis and radiation tolerance through PDCD4 ubiquitination. Journal of experimental & clinical cancer research : CR 93 30760284
2007 Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma. Oncology reports 93 17143488
2019 DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation. Journal of experimental & clinical cancer research : CR 92 31409387
2016 MiRNA-183-5p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting the PDCD4. Reproductive biology 86 27476679
2003 Programmed cell death protein 4 (pdcd4): a novel target for antineoplastic therapy? Biology of the cell 76 14630388
2009 Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer. Molecular cancer 74 19728867
2007 Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncology reports 73 17982621
2016 SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition. Apoptosis : an international journal on programmed cell death 68 26659076
2011 Tumor suppressor protein Pdcd4 inhibits translation of p53 mRNA. The Journal of biological chemistry 68 22033922
2008 siRNA-mediated knockdown of Pdcd4 expression causes upregulation of p21(Waf1/Cip1) expression. Oncogene 67 18427550
2017 MicroRNA-150 promotes cell proliferation, migration, and invasion of cervical cancer through targeting PDCD4. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 66 29091902
2014 The PDCD4/miR-21 pathway in medullary thyroid carcinoma. Human pathology 66 25316501
2011 MicroRNA-21 and PDCD4 expression in colorectal cancer. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 66 21546206
2017 Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma. Oncogene 60 28692058
2016 Quercetin inhibits Cr(VI)-induced malignant cell transformation by targeting miR-21-PDCD4 signaling pathway. Oncotarget 58 28881718
1999 Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody. Pathology international 57 10632927
2010 Have tumor suppressor PDCD4 and its counteragent oncogenic miR-21 gone rogue? Molecular interventions 55 20368367
2016 Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice. Cell death & disease 53 26775706
2017 Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene. Oncotarget 52 28423589
2015 Targeting strategies on miRNA-21 and PDCD4 for glioblastoma. Archives of biochemistry and biophysics 52 26142886
2014 Oxidative stress upregulates PDCD4 expression in patients with gastric cancer via miR-21. Current pharmaceutical design 48 23888942
2012 Tumour suppressive function and modulation of programmed cell death 4 (PDCD4) in ovarian cancer. PloS one 48 22272332
2002 Up-regulation of PDCD4 in senescent human diploid fibroblasts. Biochemical and biophysical research communications 48 12054647
2001 The chicken Pdcd4 gene is regulated by v-Myb. Oncogene 46 11313950
2017 microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma. Journal of molecular cell biology 45 28655163
2020 LncRNA-GAS5 regulates PDCD4 expression and mediates myocardial infarction-induced cardiomyocytes apoptosis via targeting MiR-21. Cell cycle (Georgetown, Tex.) 43 32308118
2020 Programmed cell death factor 4 (PDCD4), a novel therapy target for metabolic diseases besides cancer. Free radical biology & medicine 43 32745771
2017 MiR-155 inhibits proliferation and invasion by directly targeting PDCD4 in non-small cell lung cancer. Thoracic cancer 43 28842954
2020 miR-155 is high-expressed in polycystic ovarian syndrome and promotes cell proliferation and migration through targeting PDCD4 in KGN cells. Artificial cells, nanomedicine, and biotechnology 42 31851829
2019 MicroRNA‑21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c‑Jun (AP‑1) signalling pathway. International journal of oncology 42 31789394
2013 Tumor suppressor gene PDCD4 negatively regulates autophagy by inhibiting the expression of autophagy-related gene ATG5. Autophagy 42 23486359
2004 Programmed cell death protein 4 (PDCD4) acts as a tumor suppressor in neuroendocrine tumor cells. Annals of the New York Academy of Sciences 42 15153438
2012 PDCD4 expression inversely correlated with miR-21 levels in gastric cancers. Journal of cancer research and clinical oncology 41 22212233
2018 Linc00472 suppresses proliferation and promotes apoptosis through elevating PDCD4 expression by sponging miR-196a in colorectal cancer. Aging 39 29930217
2016 miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer. Oncotarget 39 27634902
2014 Pdcd4 modulates markers of macrophage alternative activation and airway remodeling in antigen-induced pulmonary inflammation. Journal of leukocyte biology 39 25097194
2016 PDCD4 Deficiency Aggravated Colitis and Colitis-associated Colorectal Cancer Via Promoting IL-6/STAT3 Pathway in Mice. Inflammatory bowel diseases 38 26891257
2018 Berberine regulates the microRNA-21-ITGΒ4-PDCD4 axis and inhibits colon cancer viability. Oncology letters 36 29564000
2018 PDCD4 suppresses proliferation, migration, and invasion of endometrial cells by inhibiting autophagy and NF-κB/MMP2/MMP9 signal pathway. Biology of reproduction 35 29912279
2018 The mechanisms and clinical significance of PDCD4 in colorectal cancer. Gene 35 30243936
2016 MicroRNA-21 and PDCD4 expression during in vitro oocyte maturation in pigs. Reproductive biology and endocrinology : RB&E 35 27084064
2010 Programmed cell death 4 (PDCD4) expression during multistep Barrett's carcinogenesis. Journal of clinical pathology 35 20702469
2022 Dissecting the Roles of PDCD4 in Breast Cancer. Frontiers in oncology 34 35795053
2018 PDCD4 Is an Androgen-Repressed Tumor Suppressor that Regulates Prostate Cancer Growth and Castration Resistance. Molecular cancer research : MCR 34 30518628
2018 Long non-coding RNA LINC00472 suppresses hepatocellular carcinoma cell proliferation, migration and invasion through miR-93-5p/PDCD4 pathway. Clinics and research in hepatology and gastroenterology 34 30522853
2014 MicroRNA-21 Down-regulates Rb1 Expression by Targeting PDCD4 in Retinoblastoma. Journal of Cancer 34 25520758
2020 microRNA-199a-3p inhibits hepatic apoptosis and hepatocarcinogenesis by targeting PDCD4. Oncogenesis 33 33099584
2012 Pdcd4 knockdown up-regulates MAP4K1 expression and activation of AP-1 dependent transcription through c-Myc. Biochimica et biophysica acta 33 22801218
2016 Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer. Oncology research 32 26802652
2020 The mTORC1/S6K/PDCD4/eIF4A Axis Determines Outcome of Mitotic Arrest. Cell reports 30 33027666
2018 MicroRNA-421-targeted PDCD4 regulates breast cancer cell proliferation. International journal of molecular medicine 30 30365117
2016 SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation. Biochemical and biophysical research communications 28 26773498
2017 Effects of Trimetazidine on PDCD4/NF-κB/TNF-α Pathway in Coronary Microembolization. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 28683436
2012 PTEN and PDCD4 are bona fide targets of microRNA-21 in human cholangiocarcinoma. Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih 27 22770403
2021 Long non-coding RNA KCNQ1OT1 increases the expression of PDCD4 by targeting miR-181a-5p, contributing to cardiomyocyte apoptosis in diabetic cardiomyopathy. Acta diabetologica 26 33907874
2020 Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway. Journal of cell science 25 33097608
2020 LncRNA PDCD4-AS1 alleviates triple negative breast cancer by increasing expression of IQGAP2 via miR-10b-5p. Translational oncology 25 33248413
2020 PDCD4 inhibits lung tumorigenesis by the suppressing p62-Nrf2 signaling pathway and upregulating Keap1 expression. American journal of cancer research 24 32195018
2019 PDCD4 Knockdown Induces Senescence in Hepatoma Cells by Up-Regulating the p21 Expression. Frontiers in oncology 23 30687637
2008 Pdcd4 protein and mRNA level alterations do not correlate in human lung tumors. Lung cancer (Amsterdam, Netherlands) 23 18457901
2017 A tyrosine kinase-STAT5-miR21-PDCD4 regulatory axis in chronic and acute myeloid leukemia cells. Oncotarget 22 29100302
2016 Pdcd4 restrains the self-renewal and white-to-beige transdifferentiation of adipose-derived stem cells. Cell death & disease 22 27031966
2015 CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation. The Journal of biological chemistry 22 25882842
2021 PDCD4 Simultaneously Promotes Microglia Activation via PDCD4-MAPK-NF-κB Positive Loop and Facilitates Neuron Apoptosis During Neuroinflammation. Inflammation 21 34613548
2020 EIF3H interacts with PDCD4 enhancing lung adenocarcinoma cell metastasis. American journal of cancer research 21 32064160
2019 MicroRNA (miRNA)-to-miRNA Regulation of Programmed Cell Death 4 (PDCD4). Molecular and cellular biology 20 31235478
2012 PDCD4 expression in thyroid neoplasia. Virchows Archiv : an international journal of pathology 20 23212265
2021 Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4. Cellular and molecular neurobiology 19 33837492
2021 Circular RNA ITCH Is a Tumor Suppressor in Clear Cell Renal Cell Carcinoma Metastasis through miR-106b-5p/PDCD4 Axis. Journal of immunology research 19 33969128
2021 circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4. Molecular therapy. Nucleic acids 19 34729247
2020 Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury. Acta pharmaceutica Sinica. B 19 33643819
2021 Hsa_circ_0053063 inhibits breast cancer cell proliferation via hsa_circ_0053063/hsa-miR-330-3p/PDCD4 axis. Aging 18 33744861
2017 miR‑21 attenuates contrast‑induced renal cell apoptosis by targeting PDCD4. Molecular medicine reports 18 28901491
2020 RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA. The Journal of biological chemistry 17 33288677
2019 Hyperandrogen enhances apoptosis of human ovarian granulosa cells via up-regulation and demethylation of PDCD4. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 16 31423917
2016 Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study. Medicine 16 26871813
2024 Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit. Nature communications 15 39117603
2022 LncRNA SLC16A1-AS1 regulates the miR-182/PDCD4 axis and inhibits the triple-negative breast cancer cell cycle. Immunopharmacology and immunotoxicology 15 35316129
2022 BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition. International journal of molecular sciences 15 35955412
2021 Repressing PDCD4 activates JNK/ABCG2 pathway to induce chemoresistance to fluorouracil in colorectal cancer cells. Annals of translational medicine 15 33569416
2019 Aberrant Expression Of PDCD4/eIF4A1 Signal Predicts Postoperative Recurrence For Early-Stage Oral Squamous Cell Carcinoma. Cancer management and research 15 31807078
2022 Pdcd4 promotes lipid deposition by attenuating PPARα-mediated fatty acid oxidation in hepatocytes. Molecular and cellular endocrinology 14 35051553
2022 Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy. Tissue & cell 14 35279605
2021 The role of lncRNA-MEG/miR-21-5p/PDCD4 axis in spinal cord injury. American journal of translational research 14 33594315
2021 Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression. BMC cancer 14 33726686
2021 miR-21 promotes the fibrotic properties in oral mucosa through targeting PDCD4. Journal of dental sciences 14 35756803
2020 MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma. Bioscience reports 14 33078826
2011 Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers. Oncology reports 14 21894439
2024 Microglial Pdcd4 deficiency mitigates neuroinflammation-associated depression via facilitating Daxx mediated PPARγ/IL-10 signaling. Journal of neuroinflammation 13 38822367
2022 eIF4A/PDCD4 Pathway, a Factor for Doxorubicin Chemoresistance in a Triple-Negative Breast Cancer Cell Model. Cells 13 36552834

Missed literature

Know a paper Affinage missed for PDCD4? Flag it for the maintainers and the community.

No submissions yet.