Affinage

PDCD5

Programmed cell death protein 5 · UniProt O14737

Length
125 aa
Mass
14.3 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDCD5 is a stress-responsive regulatory protein with dual roles as a pro-apoptotic effector and a state-specific cofactor of the TRiC/CCT chaperonin (PMID:9920759, PMID:39663456). In its apoptotic role, PDCD5 rapidly translocates from cytoplasm to nucleus early in apoptosis, preceding phosphatidylserine externalization and DNA fragmentation (PMID:11741587), where it operates as a positive regulator of the p53 pathway: it binds p53 directly, antagonizes Mdm2-mediated ubiquitination and nuclear export, displaces p53 from the p53–Mdm2 complex, promotes Mdm2 degradation, and is required for p53 phosphorylation, p21 induction, and G1 arrest after DNA damage (PMID:22914926). PDCD5 also binds and stabilizes the Tip60 acetyltransferase, enhancing Tip60-mediated K120 acetylation of p53 and cooperatively accelerating DNA damage-induced apoptosis (PMID:19308289). In parallel it engages the mitochondrial apoptotic axis, facilitating Bax translocation, permeability transition pore opening, and cytochrome c release (PMID:12019438, PMID:16374546). PDCD5 abundance is set by an extensive post-translational network: CK2 phosphorylation at Ser118 is activating (PMID:19616514), whereas PPEF-1 dephosphorylation at Ser119 destabilizes it (PMID:28051100); OTUD5 deubiquitinates PDCD5 at K97/98 and YAF2 and STK31 block its proteasomal turnover to enable p53 activation (PMID:25499082, PMID:25603536, PMID:30144069), while DNAJB1 and JMJD4 promote its degradation (PMID:25444898, PMID:39567206). Lgr5 sequesters PDCD5 from the nucleus to blunt p53 stabilization and confer chemoresistance (PMID:31244936). Distinct from apoptosis, PDCD5 binds the open state of TRiC via its C-terminus and promotes folded-substrate release by competing with PhLP2A, a function essential for flagellum biogenesis and ciliogenesis (PMID:39663456, PMID:41506263). In the immune system PDCD5 directs T-cell fate epigenetically by stabilizing TOX2 and activating PRDM9 to deposit permissive H3K4me3 at the Tbx21 (T-bet) locus, programming iNKT1 and CD8+ effector differentiation (PMID:29921968, PMID:40111008), and it cooperates with Tip60 to acetylate FOXP3 in regulatory T cells (PMID:24012345). PDCD5 is essential in development, as germline knockout causes mid-gestation embryonic lethality from placental dysplasia (PMID:28542142).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 Medium

    Established PDCD5 as a bona fide pro-apoptotic gene, defining the founding functional hypothesis for all subsequent mechanism.

    Evidence cDNA-RDA cloning from apoptotic leukemia cells and overexpression death assays in tumor cells

    PMID:9920759

    Open questions at the time
    • Overexpression-only; no endogenous mechanism
    • No molecular partner identified
  2. 2001 Medium

    Resolved when and where PDCD5 acts by showing stimulus-independent nuclear translocation that precedes downstream apoptotic hallmarks, implying an early regulatory step.

    Evidence Immunofluorescence, subcellular fractionation and live imaging across multiple cell lines and stimuli

    PMID:11741587

    Open questions at the time
    • Translocation trigger and nuclear target unknown at the time
    • Does not establish causality versus correlation with apoptosis
  3. 2002 Medium

    Demonstrated endogenous PDCD5 is required, not merely sufficient, for apoptosis acceleration, and placed it functionally at the mitochondrion.

    Evidence Intracellular anti-PDCD5 antibody electroporation and in vitro isolated-mitochondria PTP/cytochrome c assays

    PMID:12019438 PMID:12151055

    Open questions at the time
    • Mechanism of mitochondrial action undefined
    • No direct mitochondrial protein partner identified
  4. 2006 High

    Defined how exogenous PDCD5 enters cells, mapping a heparan-sulfate/lipid-raft uptake route and the residues 109-115 translocation determinant relevant to its candidate therapeutic delivery.

    Evidence Endocytosis assays with dominant-negatives, raft disruption, EM and deletion mutagenesis; heparin-binding quantification by capillary electrophoresis

    PMID:16754680 PMID:17165023

    Open questions at the time
    • Physiological relevance of cell entry versus intracellular function unclear
    • Receptor identity beyond HSPG not defined
  5. 2006 Medium

    Positioned PDCD5 upstream of the mitochondrial apoptotic core by showing it is required for Bax translocation, cytochrome c release and caspase-3 activation.

    Evidence siRNA knockdown with cytochrome c fractionation, caspase assays and Bax localization in Bax-overexpression apoptosis

    PMID:16374546

    Open questions at the time
    • Direct biochemical link between PDCD5 and Bax not shown
    • Endogenous-stimulus dependence not tested
  6. 2009 High

    Identified the first chromatin-level effector mechanism: PDCD5 stabilizes and activates Tip60 to acetylate p53-K120, coupling PDCD5 to the DNA damage response.

    Evidence Reciprocal Co-IP, GST-pulldown, in vitro HAT assays and UV-irradiation apoptosis with knockdown

    PMID:19308289

    Open questions at the time
    • Whether Tip60 binding is universal across cell types unresolved
    • Structural basis of Tip60 stabilization unknown
  7. 2009 High

    Established phospho-regulation of PDCD5 activity, showing CK2 phosphorylation of Ser118 is required for its apoptosis-accelerating function.

    Evidence In vitro CK2 kinase assay, mass-spec phosphosite mapping and S118A mutant apoptosis assays; yeast homolog NMR triple-helix structure with pro-apoptotic mutagenesis

    PMID:19469552 PMID:19616514

    Open questions at the time
    • How Ser118 phosphorylation alters PDCD5 behavior mechanistically not defined
    • Human full-length structure not solved
  8. 2012 High

    Delineated the core p53-stabilizing mechanism: PDCD5 binds p53, antagonizes Mdm2-mediated ubiquitination/export, and drives Mdm2 degradation, explaining its DNA-damage checkpoint role.

    Evidence GST-pulldown, Co-IP, ubiquitination assays, ChIP, RNAi and cell-cycle analysis

    PMID:22914926

    Open questions at the time
    • Mechanism by which PDCD5 promotes Mdm2 degradation not fully defined
    • Direct versus indirect competition for p53 not structurally resolved
  9. 2014 High

    Opened the post-translational stability axis, identifying DNAJB1 as a destabilizer and OTUD5 as a DNA-damage-induced deubiquitinase that stabilizes PDCD5 at K97/98 to license sequential p53 activation.

    Evidence Yeast two-hybrid, Co-IP, ubiquitination/deubiquitination assays, site-directed mutants and rescue apoptosis assays

    PMID:25444898 PMID:25499082

    Open questions at the time
    • Upstream signals controlling OTUD5/DNAJB1 engagement unclear
    • Quantitative contribution of each regulator in vivo not established
  10. 2015 High

    Expanded the stabilizer network (YAF2) and revealed essential developmental and immunoregulatory functions, including embryonic lethality from placental dysplasia and FOXP3 acetylation in Tregs.

    Evidence Yeast two-hybrid/Co-IP for YAF2, conditional knockout mouse with histopathology, and transgenic mouse EAE/Treg polarization studies

    PMID:24012345 PMID:25603536 PMID:28542142

    Open questions at the time
    • Whether placental phenotype reflects p53 or apoptosis-independent roles unresolved
    • Tissue-specific requirement versus systemic role not separated
  11. 2015 Medium

    Provided a contrasting negative result, finding PDCD5 dispensable for DNA-damage apoptosis in several lines and failing to confirm the Tip60 interaction, qualifying the universality of the p53/Tip60 model.

    Evidence Conditional shRNA ablation across cell types with genotoxic-stress apoptosis assays and Co-IP

    PMID:26062895

    Open questions at the time
    • Cell-type context dependence not reconciled with positive studies
    • Does not exclude redundancy masking a requirement
  12. 2017 High

    Closed the phospho-regulatory loop by identifying PPEF-1 as the phosphatase that dephosphorylates Ser119 to destabilize PDCD5, counterbalancing CK2.

    Evidence Co-IP, in vitro phosphatase assay, catalytic-dead PPEF-1 mutant and stability/apoptosis assays

    PMID:28051100

    Open questions at the time
    • Relationship between Ser118 and Ser119 phospho-states not integrated
    • Upstream control of PPEF-1 activity unknown
  13. 2018 High

    Revealed an epigenetic effector mechanism in immunity: PDCD5 stabilizes TOX2 to deposit H3K4me3 at the Tbx21 promoter, controlling iNKT1 lineage fate via T-bet.

    Evidence T-cell-specific Pdcd5 knockout, flow cytometry, H3K4me3 ChIP and PDCD5-TOX2 Co-IP

    PMID:29921968

    Open questions at the time
    • Whether TOX2 stabilization uses the same machinery as p53 regulation unknown
    • Direct biochemical mechanism of histone-mark deposition not shown
  14. 2018 Medium

    Added STK31 as a stabilizing kinase-family interactor that activates PDCD5-mediated p53 apoptotic signaling.

    Evidence Co-IP, stability Western blots and PDCD5-dependent apoptosis epistasis

    PMID:30144069

    Open questions at the time
    • Whether STK31 phosphorylates PDCD5 directly not tested
    • Single-lab Co-IP without reciprocal validation
  15. 2019 High

    Identified Lgr5 as a sequestering partner that blocks PDCD5 nuclear translocation to suppress p53 and confer hepatocellular carcinoma chemoresistance, linking PDCD5 regulation to drug response.

    Evidence Yeast two-hybrid, reciprocal Co-IP/GST-pulldown, fractionation and in vitro/in vivo chemoresistance assays

    PMID:31244936

    Open questions at the time
    • Stoichiometry and dynamics of Lgr5-PDCD5 sequestration not quantified
    • Generality across tumor types untested
  16. 2024 High

    Reframed PDCD5 beyond apoptosis by showing it is a state-selective cofactor that binds the open TRiC/CCT chaperonin at a position overlapping substrate and prefoldin sites.

    Evidence In-cell cryo-electron tomography resolving TRiC conformational states in human cells

    PMID:39663456

    Open questions at the time
    • Functional consequence of TRiC binding not established in this study
    • Link between chaperonin and apoptotic roles unclear
  17. 2025 High

    Defined the chaperonin mechanism and its physiology: PDCD5 promotes TRiC substrate release by competing with PhLP2A via its C-terminus, a step essential for flagellum and ciliary biogenesis.

    Evidence Mouse knockout, near-atomic cryo-EM of PDCD5-TRiC, PDCD5-vs-PhLP2A competition assay, mass-spec of trapped substrates and C-terminal deletion

    PMID:41506263

    Open questions at the time
    • How a single protein serves both nuclear/apoptotic and chaperonin roles unresolved
    • Substrate spectrum of PDCD5-dependent release incompletely defined
  18. 2025 High

    Extended the epigenetic-programming theme to PRDM9 and CD8+ effector fate, and added new apoptotic regulators (JMJD4) and a mitochondrial role in airway injury, broadening PDCD5's functional reach.

    Evidence Conditional Pdcd5 knockout, PDCD5-PRDM9 Co-IP, ChIP/ATAC-seq; LC-MS/Co-IP for JMJD4; siRNA with mitochondrial ROS/membrane-potential readouts in airway cells

    PMID:39567206 PMID:40111008 PMID:41447117

    Open questions at the time
    • Whether PRDM9/TOX2 epigenetic pathways converge mechanistically unknown
    • JMJD4 and airway findings are single-lab with limited orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PDCD5's nuclear p53/apoptotic activity, its TRiC chaperonin cofactor function, and its epigenetic T-cell programming are mechanistically and structurally partitioned within one small protein.
  • No unified structural model reconciling the distinct interaction surfaces
  • Signals that route PDCD5 between these functions are unknown
  • Relative physiological weighting of each role across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
DNAJB1MDM2OTUD5PPEF-1TIP60 (KAT5)TOX2TP53YAF2
Complex memberships
TRiC/CCT chaperonin (open-state cofactor)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PDCD5 (TFAR19) is a novel apoptosis-promoting protein cloned from TF-1 leukemia cells undergoing apoptosis; overexpression enhances apoptosis triggered by growth factor or serum deprivation in tumor cells, establishing a direct pro-apoptotic role. cDNA-RDA cloning, overexpression in tumor cells, cell death assays Biochemical and biophysical research communications Medium 9920759
2001 PDCD5 undergoes rapid nuclear translocation from cytoplasm to nucleus during apoptosis, preceding phosphatidylserine externalization and DNA fragmentation, and occurring in parallel with mitochondrial membrane potential loss; this translocation is independent of cell type and apoptotic stimulus. Immunofluorescence, subcellular fractionation, live-cell imaging in multiple cell lines with diverse apoptotic stimuli FEBS letters Medium 11741587
2002 Introduction of anti-PDCD5 monoclonal antibody into HeLa cells by in situ electroporation suppresses the apoptosis-accelerating effect of endogenous PDCD5, demonstrating that endogenous PDCD5 is required for its pro-apoptotic function. In situ electroporation of antibody into living cells, flow cytometry apoptosis assay Life sciences Medium 12151055
2002 Recombinant TFAR19/PDCD5 protein facilitates opening of the mitochondrial permeability transition pore (PTP), decreases mitochondrial membrane potential, and promotes cytochrome c release in isolated mitochondria, indicating a direct functional role at the mitochondria. In vitro assay with isolated mitochondria, measurement of PTP opening, membrane potential, and cytochrome c release Acta biochimica et biophysica Sinica Medium 12019438
2004 Overexpression of TAJ/TROY (a TNF receptor superfamily member) induces paraptotic cell death, which is enhanced by PDCD5 overexpression; endogenous PDCD5 is upregulated in response to TAJ/TROY overexpression, placing PDCD5 as a regulator in both apoptotic and non-apoptotic programmed cell death. Overexpression in 293T cells, transmission electron microscopy, flow cytometry, co-expression assays Journal of cell science Medium 15020679
2006 siRNA knockdown of PDCD5 attenuates Bax-overexpression-induced apoptosis, inhibits caspase-3 activation, and reduces cytochrome c release from mitochondria; it also reduces Bax translocation from cytosol to mitochondria, placing PDCD5 upstream of the mitochondrial apoptosis pathway acting through Bax translocation. siRNA knockdown, Western blot, flow cytometry, cytochrome c fractionation, caspase-3 activity assay Apoptosis Medium 16374546
2006 Exogenous PDCD5 protein is taken up by cells via a clathrin-independent endocytic pathway involving heparan sulfate proteoglycan binding and lipid rafts; deletion mutagenesis mapped the translocation activity to residues 109–115 of PDCD5. Endocytosis assays with fluorescent PDCD5, clathrin dominant-negative mutant, lipid raft disruption drugs, sucrose density centrifugation, electron microscopy, deletion mutagenesis The Journal of biological chemistry High 16754680
2006 PDCD5 binds heparin with a binding constant of 4.17×10⁴ M⁻¹ as determined by Scatchard analysis; PDCD5-related peptides also interact with heparin, consistent with heparan sulfate proteoglycan-mediated cell entry. Capillary zone electrophoresis (CZE), Scatchard analysis Analytical and bioanalytical chemistry Medium 17165023
2009 PDCD5 physically binds to Tip60 histone acetyltransferase (HAT); PDCD5 enhances Tip60 protein stability, increases Tip60 HAT activity, promotes Tip60-dependent histone acetylation, and increases Tip60-mediated K120 acetylation of p53. After UV irradiation the PDCD5–Tip60 complex increases and cooperatively accelerates DNA damage-induced apoptosis. Co-immunoprecipitation, GST-pulldown, HAT activity assays, Western blot for p53-K120 acetylation, siRNA knockdown, UV irradiation apoptosis assay Neoplasia High 19308289
2009 PDCD5 is phosphorylated by CK2 kinase at Ser118 both in vitro and in 293T cells; the non-phosphorylatable S118A mutant impairs PDCD5's ability to accelerate doxorubicin- or UV-induced apoptosis in U2OS cells. In vitro kinase assay with CK2α and holoenzyme, mass spectrometry identification of phospho-S118, transfection of S118A mutant, apoptosis assay Biochemical and biophysical research communications High 19616514
2009 The yeast PDCD5 homolog Ymr074cP (N116 fragment) adopts a triple-helix bundle fold as determined by NMR; overexpression of Ymr074c promotes H₂O₂-induced apoptosis in yeast in both a metacaspase Yca1-dependent and Yca1-independent manner, and deletion of the N-terminal helix attenuates its pro-apoptotic activity. Heteronuclear NMR solution structure, spin-label experiments, yeast overexpression, Yca1 deletion epistasis Biochemistry High 19469552
2012 PDCD5 directly binds p53 (shown by GST-pulldown, co-immunoprecipitation, and co-localization); PDCD5 enhances p53 stability by antagonizing Mdm2-induced ubiquitination, nuclear export and proteasomal degradation, displaces p53 from the p53–Mdm2 complex, and directly promotes Mdm2 degradation. PDCD5 is also required for proper G1 arrest and p53 phosphorylation (Ser9, 20, 392) and p21 expression after DNA damage. GST-pulldown, co-immunoprecipitation, co-localization, ubiquitination assay, RNAi knockdown, chromatin immunoprecipitation (ChIP), cell cycle analysis Apoptosis High 22914926
2014 DNAJB1 interacts with PDCD5 (identified by yeast two-hybrid, confirmed by Co-IP) via its D5 domain (Δ180-210) and induces ubiquitin-dependent proteasomal degradation of PDCD5, thereby inhibiting p53-mediated apoptosis; DNAJB1 knockdown increases etoposide-induced p53-pathway apoptosis in a PDCD5-dependent manner. Yeast two-hybrid screen, Co-IP, domain mapping, ubiquitination assay, siRNA knockdown, colony formation and apoptosis assays Cancer letters High 25444898
2014 OTUD5 deubiquitinase binds PDCD5 in response to DNA damage (etoposide treatment) and stabilizes PDCD5 by deubiquitinating it at Lys-97/98; OTUD5-dependent PDCD5 stabilization is required for sequential p53 activation. PDCD5 mutants defective for OTUD5 interaction (E94D) or p53 interaction (E16D) fail to facilitate p53 activation. Co-immunoprecipitation, ubiquitination/deubiquitination assay, site-directed mutagenesis, knockdown and rescue experiments, apoptosis assays Cancer letters High 25499082
2015 YAF2 (YY1-associated factor 2) binds PDCD5 (identified by yeast two-hybrid, confirmed by Co-IP) and stabilizes PDCD5 by blocking ubiquitin-dependent proteasomal degradation; YAF2 promotes p53 activation via PDCD5. PDCD5 mutants defective for YAF2 interaction (E4D) or p53 interaction (E16D) cannot rescue impaired apoptosis upon PDCD5 ablation. Yeast two-hybrid, Co-IP, ubiquitination assay, siRNA knockdown, domain mutagenesis, apoptosis assay Biochimica et biophysica acta High 25603536
2015 PDCD5 knockout in mice causes embryonic lethality at mid-gestation due to placental dysplasia (defective spongiotrophoblasts and trophoblast giant cells); PDCD5-knockout MEFs show increased apoptosis, G0/G1 arrest, and decreased VEGF/HGF and Pik3ca-Akt-mTOR pathway activity. Conditional knockout mouse model, histopathology, Western blot, cell cycle analysis Cell death & disease High 28542142
2015 PDCD5 interacts with FOXP3 and increases FOXP3 acetylation in synergy with Tip60, enhancing the repressive function of FOXP3 in regulatory T cells; PDCD5 transgenic mice show increased Treg frequency, enhanced TGF-β-induced Treg polarization, and reduced autoimmune encephalomyelitis severity. Co-immunoprecipitation, acetylation assay, PDCD5 transgenic mice, EAE model, T cell polarization assay, flow cytometry Journal of autoimmunity High 24012345
2017 Serine/threonine phosphatase PPEF-1 physically interacts with PDCD5 and dephosphorylates it at Ser-119, leading to PDCD5 destabilization; catalytically inactive PPEF-1D172N does not suppress CK2α-mediated PDCD5 stabilization or p53-mediated apoptosis, demonstrating phosphatase activity is required. Co-immunoprecipitation, in vitro phosphatase assay, site-directed mutagenesis of PPEF-1 active site, Western blot stability assays, knockdown/overexpression apoptosis assays Scientific reports High 28051100
2018 T cell-specific PDCD5 deletion in mice abolishes the iNKT1 lineage by reducing T-bet expression in early thymic iNKT cells; PDCD5 stabilizes TOX2 (a high mobility group protein), which promotes permissive H3K4me3 modification at the Tbx21 (T-bet) promoter, linking PDCD5 to epigenetic regulation of iNKT1 fate. Conditional T cell Pdcd5 knockout mouse, flow cytometry, ChIP for H3K4me3, Co-immunoprecipitation of PDCD5-TOX2 Cellular & molecular immunology High 29921968
2018 STK31 (serine/threonine kinase 31) interacts with PDCD5 and stabilizes PDCD5 protein; STK31 overexpression activates PDCD5-mediated p53 apoptotic signaling in response to etoposide, while STK31 depletion impairs this pathway in a PDCD5-dependent manner. Co-immunoprecipitation, Western blot stability assay, overexpression and knockdown with apoptosis assays, colony formation assay Journal of cellular physiology Medium 30144069
2019 Lgr5 directly binds PDCD5 via its N-terminal extracellular domain (shown by Co-IP and GST-pulldown); Lgr5 blocks nuclear translocation of PDCD5, thereby preventing PDCD5-dependent p53 stabilization and causing p53 degradation, leading to doxorubicin resistance in hepatocellular carcinoma. Yeast two-hybrid, Co-IP, GST-pulldown, nuclear/cytoplasmic fractionation, ubiquitination assay, in vitro and in vivo chemoresistance assays Theranostics High 31244936
2024 Cryo-electron tomography in human cells reveals that PDCD5 specifically binds to the open (but not closed) state of the TRiC/CCT chaperonin complex, at a position compatible with both substrate and prefoldin binding, suggesting PDCD5 is a state-specific cofactor of TRiC. Cryo-electron tomography (in situ), structural analysis of TRiC states in intact human cells Nature High 39663456
2025 PDCD5 is required for flagellum biogenesis in spermatids and ciliogenesis in mouse ciliated cells; structural studies show PDCD5 interacts with open-state TRiC and promotes substrate release by competing with PhLP2A for TRiC binding; PDCD5 depletion traps flagellum- and cilium-associated proteins inside TRiC. The C-terminus of PDCD5 is required for TRiC interaction and this function. Mouse PDCD5 knockout, cryo-EM structures of PDCD5-TRiC at near-atomic resolution, competitive binding assay (PDCD5 vs. PhLP2A), mass spectrometry of trapped TRiC substrates, C-terminal deletion mutagenesis Molecular cell High 41506263
2025 PDCD5 interaction with PRDM9 promotes nuclear translocation and lysine methyltransferase activity of PRDM9, leading to H3K4me3 modification of effector-phenotype genes (including Tbx21) in CD8+ T cells; Pdcd5 deletion impairs CD8+ effector T cell differentiation and chromatin accessibility at Tbx21 and its target genes without affecting T cell activation, metabolic reprogramming, or memory/exhaustion. Conditional Pdcd5 knockout in T cells, Co-immunoprecipitation of PDCD5-PRDM9, ChIP for H3K4me3 and chromatin accessibility (ATAC-seq), chronic viral infection mouse model European journal of immunology High 40111008
2025 PDCD5 contributes to airway epithelial cell damage via the mitochondrial pathway; PDCD5 silencing attenuates cigarette smoke extract (CSE)-induced mitochondrial ROS accumulation, mitochondrial membrane potential loss, intracellular ATP depletion, and mitochondrial structural damage in airway epithelial cells. siRNA knockdown, ROS measurement, JC-1 membrane potential assay, ATP measurement, transmission electron microscopy, apoptosis assay The Kaohsiung journal of medical sciences Medium 41447117
2025 JMJD4 directly interacts with PDCD5 (identified by LC-MS, confirmed by Co-IP) and negatively regulates PDCD5 protein levels, thereby suppressing the PDCD5-TP53 apoptotic pathway and promoting cancer cell proliferation and chemo-resistance. Liquid chromatography–mass spectrometry (LC-MS) interactome, Co-immunoprecipitation, Western blot, colony-formation assay, apoptosis assay BMB reports Medium 39567206
2015 A study using conditional shRNA ablation of PDCD5 in multiple cell types found that PDCD5 was dispensable for DNA damage-induced apoptosis and cell cycle arrest; while PDCD5–p53 interaction was confirmed, PDCD5–Tip60 interaction could not be confirmed in these cell lines. This constitutes a NEGATIVE finding challenging the universality of PDCD5 as a rate-limiting factor in the DNA damage response. Conditional shRNA cell lines, apoptosis assay after genotoxic stress, Co-IP for PDCD5–p53 and PDCD5–Tip60 Scientific reports Medium 26062895

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression. Journal of cell science 158 15020679
1999 TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal. Biochemical and biophysical research communications 137 9920759
2001 Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis? FEBS letters 90 11741587
2009 PDCD5 interacts with Tip60 and functions as a cooperator in acetyltransferase activity and DNA damage-induced apoptosis. Neoplasia (New York, N.Y.) 65 19308289
2019 Lgr5-mediated p53 Repression through PDCD5 leads to doxorubicin resistance in Hepatocellular Carcinoma. Theranostics 56 31244936
2012 PDCD5 interacts with p53 and functions as a positive regulator in the p53 pathway. Apoptosis : an international journal on programmed cell death 56 22914926
2006 Short interfering RNA against the PDCD5 attenuates cell apoptosis and caspase-3 activity induced by Bax overexpression. Apoptosis : an international journal on programmed cell death 55 16374546
2022 Human Amniotic Fluid Mesenchymal Stem Cell-Derived Exosomes Inhibit Apoptosis in Ovarian Granulosa Cell via miR-369-3p/YAF2/PDCD5/p53 Pathway. Oxidative medicine and cellular longevity 54 35936223
2002 Transfer of anti-TFAR19 monoclonal antibody into HeLa cells by in situ electroporation can inhibit the apoptosis. Life sciences 48 12151055
2013 The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury. CNS neuroscience & therapeutics 46 23638963
2014 DNAJB1 destabilizes PDCD5 to suppress p53-mediated apoptosis. Cancer letters 42 25444898
2008 Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas. Oncology reports 41 18695908
2014 Deubiquitinase OTUD5 mediates the sequential activation of PDCD5 and p53 in response to genotoxic stress. Cancer letters 39 25499082
2010 Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo. Apoptosis : an international journal on programmed cell death 39 20349137
2006 Cellular uptake of exogenous human PDCD5 protein. The Journal of biological chemistry 34 16754680
2013 PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T cells and suppressing Th17 and Th1 responses. Journal of autoimmunity 33 24012345
2012 The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells. Cellular signalling 31 22560879
2008 Adenovirus-mediated PDCD5 gene transfer sensitizes K562 cells to apoptosis induced by idarubicin in vitro and in vivo. Apoptosis : an international journal on programmed cell death 30 18401719
2007 Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis. Apoptosis : an international journal on programmed cell death 29 17468978
2010 Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells. Biochemical and biophysical research communications 28 20398626
2009 Programmed cell death protein 5 (PDCD5) is phosphorylated by CK2 in vitro and in 293T cells. Biochemical and biophysical research communications 25 19616514
2014 NF-κB p65 recruited SHP regulates PDCD5-mediated apoptosis in cancer cells. Apoptosis : an international journal on programmed cell death 24 24343129
2012 PDCD5 promotes cisplatin-induced apoptosis of glioma cells via activating mitochondrial apoptotic pathway. Cancer biology & therapy 24 22688731
2017 PDCD5 regulates cell proliferation, cell cycle progression and apoptosis. Oncology letters 23 29403562
2020 OTU deubiquitinase 5 inhibits the progression of non-small cell lung cancer via regulating p53 and PDCD5. Chemical biology & drug design 22 32248621
2017 Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5. Scientific reports 19 28051100
2014 Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats. Neuroscience letters 19 24614334
2013 Plasma and synovial fluid programmed cell death 5 (PDCD5) levels are inversely associated with TNF-α and disease activity in patients with rheumatoid arthritis. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 19 23327497
2010 Transfection of PDCD5 sensitizes colorectal cancer cells to cisplatin-induced apoptosis in vitro and in vivo. European journal of pharmacology 19 20869960
2009 A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines. Apoptosis : an international journal on programmed cell death 19 19551515
2015 PDCD5 protects against cardiac remodeling by regulating autophagy and apoptosis. Biochemical and biophysical research communications 18 25881505
2013 PDCD5 expression predicts a favorable outcome in patients with hepatocellular carcinoma. International journal of oncology 18 23807738
2024 In situ analysis reveals the TRiC duty cycle and PDCD5 as an open-state cofactor. Nature 16 39663456
2015 Recombinant human PDCD5 (rhPDCD5) protein is protective in a mouse model of multiple sclerosis. Journal of neuroinflammation 16 26068104
2013 Serum programmed cell death protein 5 (PDCD5) levels is upregulated in liver diseases. Journal of immunoassay & immunochemistry 16 23656249
2012 Transfection of PDCD5 effect on the biological behavior of tumor cells and sensitized gastric cancer cells to cisplatin-induced apoptosis. Digestive diseases and sciences 16 22359193
2013 Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo. Biochemistry and cell biology = Biochimie et biologie cellulaire 15 24219296
2011 PDCD5-regulated cell fate decision after ultraviolet-irradiation-induced DNA damage. Biophysical journal 15 22261045
2017 Deletion of Pdcd5 in mice led to the deficiency of placenta development and embryonic lethality. Cell death & disease 13 28542142
2015 Anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced model of arthritis. Inflammation 13 25178696
2014 PDCD5 transfection increases cisplatin sensitivity and decreases invasion in hepatic cancer cells. Oncology letters 12 25436001
2004 Expression of PDCD5, a novel apoptosis related protein, in human osteoarthritic cartilage. Acta pharmacologica Sinica 12 15132838
2016 Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in mice. Brain research 11 27608954
2015 PDCD5 functions as a regulator of p53 dynamics in the DNA damage response. Journal of theoretical biology 11 26433055
2015 Recombinant human PDCD5 exhibits an antitumor role in hepatocellular carcinoma cells via clathrin‑dependent endocytosis. Molecular medicine reports 11 26498344
2020 MicroRNA-766 Promotes The Proliferation, Migration And Invasion, And Inhibits The Apoptosis Of Cutaneous Squamous Cell Carcinoma Cells By Targeting PDCD5. OncoTargets and therapy 10 32494163
2018 PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision. Cellular & molecular immunology 10 29921968
2015 YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5. Biochimica et biophysica acta 10 25603536
2005 TFAR19 gene changes the biophysical properties of murine erythroleukemia cells. Cell biochemistry and biophysics 10 16247177
2022 PDCD5 inhibits progression of renal cell carcinoma by promoting T cell immunity: with the involvement of the HDAC3/microRNA-195-5p/SGK1. Clinical epigenetics 9 36266728
2014 Adenovirus-delivered PDCD5 counteracts adriamycin resistance of osteosarcoma cells through enhancing apoptosis and inhibiting Pgp. International journal of clinical and experimental medicine 9 25664052
2009 Solution structure of S. cerevisiae PDCD5-like protein and its promoting role in H(2)O(2)-induced apoptosis in yeast. Biochemistry 9 19469552
2008 The allelic distribution of a single nucleotide polymorphism in the PDCD5 gene locus of Japanese non-small cell lung cancer patients. Molecular medicine reports 9 21479467
2022 New Approach about the Signaling Crosstalk between IQGAPs/ NF- κB/IL-8 and PDCD5/p53/TRAIL Pathways that Modulate Malignant Transformation in Hepatocellular Carcinoma. Asian Pacific journal of cancer prevention : APJCP 8 35092397
2018 Serine/threonine kinase 31 promotes PDCD5-mediated apoptosis in p53-dependent human colon cancer cells. Journal of cellular physiology 8 30144069
2004 [Expression of PDCD5 in tissues of normal cervix, CIN I-III and cervical cancer]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 8 15303136
2021 The Effect of Global DNA Methylation on PDCD5 Expression in the PBMC of Occupational Chromate Exposed Workers. Journal of occupational and environmental medicine 7 34184653
2012 Construction and characterization of a PDCD5 recombinant lentivirus vector and its expression in tumor cells. Oncology reports 7 22484667
2018 The importance of expressing PDCD4 and PDCD5 anti-oncogenes in glioma. Journal of biological regulators and homeostatic agents 6 29921407
2015 The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death. Scientific reports 6 26062895
2011 Determination of PDCD5 in Peripheral Blood Serum of Cancer Patients. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 6 23467771
2006 Studies on interactions of programmed cell death 5 (PDCD5) and its related peptides with heparin by capillary zone electrophoresis. Analytical and bioanalytical chemistry 6 17165023
2005 [Apoptosis and expressions of PDCD5 and Caspase-3 in renal tissues of children with lupus nephritis]. Zhonghua er ke za zhi = Chinese journal of pediatrics 6 16083554
2002 [TFAR19 enhances the opening of permeability transition pore in the mitochondrial membrane of mice liver]. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 6 12019438
2002 Soluble expression in Escherichia coli, purification and characterization of a human TF-1 cell apoptosis-related protein TFAR19. Protein expression and purification 6 12135567
2023 Characterisation of a novel transcript LNPPS acting as tumour suppressor in bladder cancer via PDCD5-mediated p53 degradation blockage. Clinical and translational medicine 5 36578176
2023 Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro. Frontiers in physiology 5 37904794
2007 [Adenovirus-mediated PDCD5 gene transfer sensitizes apoptosis of K562 cells induced by etoposide]. Zhongguo shi yan xue ye xue za zhi 5 17956665
2005 [Expression of novel apoptosis-related protein PDCD5 in granulosa cells of polysystic ovary syndrome]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 5 16224516
2023 Cancer-testis non-coding RNA LEF1-AS1 regulates the nuclear translocation of PDCD5 and suppresses its interaction with p53 signaling: a novel target for immunotherapy in esophageal squamous cell carcinoma. Carcinogenesis 4 36827466
2021 MiR-10b-3p Protects Cerebral I/R Injury through Targeting Programmed Cell Death 5 (PDCD5). Critical reviews in eukaryotic gene expression 4 34936294
2016 The roles of serum PDCD5 in circulating CD133 positive cells of the patients with gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 4 27034262
2016 The reduced PDCD5 protein is correlated with the degree of tumor differentiation in endometrioid endometrial carcinoma. SpringerPlus 4 27398268
2012 Correlation of PDCD5 and apoptosis in hair cells and spiral ganglion neurons of different age of C57BL/6J mice. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 4 22282256
2006 [Expression of TFAR19(PDCD5) in normal human kidney, renal clear cell carcinoma, normal human bladder and bladder carcinoma]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 4 16793605
2018 Synergistic antitumoral efficacy of a novel replicative adenovirus SG611-PDCD5 and daunorubicin in human leukemic cells. OncoTargets and therapy 3 30197523
2015 Establishment of stable multiple myeloma cell line with overexpressed PDCD5 and its proapoptosis mechanism. International journal of clinical and experimental pathology 3 26617773
2007 [Abnormal expression of PDCD5 in the bone marrow cells of adult acute myeloid leukemia]. Zhongguo shi yan xue ye xue za zhi 3 17605845
2000 [Preparation and identification of monoclonal antibodies against human apoptosis-related protein TFAR19]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 3 12903389
2025 Epigenetic Regulation of CD8+ Effector T Cell Differentiation by PDCD5. European journal of immunology 2 40111008
2019 Clinicopathological Significance of Decreased Expression of the Tumor Inhibitor Gene PDCD5 in Osteoclastoma. Genetic testing and molecular biomarkers 2 31638427
2010 [Sensitizing effect of recombinant human PDCD5 protein on chemotherapy of acute monocytic leukemia cell line U937 and its mechanism]. Zhongguo shi yan xue ye xue za zhi 2 20416151
2010 [Effect of human recombinant PDCD5 protein on cell apoptosis of multiple myeloma KM3 cells induced by dexamethasone and its mechanism]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2 20693715
2008 [Expression of PDCD5 in multiple myeloma and its relation with BCL-2]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2 18812660
2007 Effects of TFAR19 gene on the in vivo biorheological properties and pathogenicity of mouse erythroleukemia cell line MEL. Science in China. Series C, Life sciences 2 17393091
2005 [Expressions of PDCD5 and p53 in oral leukoplakia and oral squamous cell carcinoma]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 2 16086069
2003 [Characterization of programmed cell death 5 (PDCD5) gene in human cartilage and its possible significance]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 2 14601303
2003 Effects of TFAR19 gene on the growth and biorheological properties of mouse erythroleukemia cell line MEL. Science in China. Series C, Life sciences 2 18763144
2000 [Expression of TFAR19 in Apoptotic Processes of Jurkat Cells Induced with Various Methods]. Zhongguo shi yan xue ye xue za zhi 2 12578691
2025 JMJD4 promotes tumor progression via inhibition of the PDCD5-TP53 pathway. BMB reports 1 39567206
2025 PDCD5 Contributes to Airway Epithelial Cell Damage via Mitochondrial Pathway and Participates in COPD Pathogenesis. The Kaohsiung journal of medical sciences 1 41447117
2020 NMR resonance assignments of the programmed cell death protein 5 (PDCD5) from Toxoplasma gondii. Biomolecular NMR assignments 1 32578164
2011 [Expression of PDCD5 and caspase 3 in the cochlea of different age of C57BL/6J mice]. Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 1 22177044
2005 [The effect of carvedilol on apoptosis gene PDCD5 expression in chronic heart failure patients]. Zhonghua yi xue za zhi 1 15932730
2004 [FTIR spectroscopy studies on the apoptosis-promoting effect of TFAR19 on the erythroleukemia cell line MEL]. Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 1 15250154
2003 [In silico data mining of the human programmed cell death 5 (PDCD5) sequences]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 1 12947547
2026 PDCD5 promotes substrate release from the TRiC complex in cilia and flagella. Molecular cell 0 41506263
2024 Association of overexpression of PLD6, CHRAC1 and PDCD5 with type 2 diabetes mellitus. Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina 0 39526719
2023 PDCD5 as a Potential Biomarker for Improved Prediction of the Incidence and Remission for Patients with Rheumatoid Arthritis. Rheumatology and therapy 0 37528307
2015 [Expression and clinical significance of PDCD5 in patients with acute myeloid leukemia]. Zhongguo shi yan xue ye xue za zhi 0 25687040

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