Affinage

PDPK1

3-phosphoinositide-dependent protein kinase 1 · UniProt O15530

Length
556 aa
Mass
63.2 kDa
Annotated
2026-06-10
61 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDPK1 is a serine/threonine kinase that occupies a central node in PI3K-AKT/mTOR signaling, transducing growth, survival, and metabolic cues by directly phosphorylating and activating multiple AGC-family kinases (PMID:25269480, PMID:32926495, PMID:39821712). It activates AKT through a required physical interaction, and disrupting the AKT1-PDPK1 interface with a small molecule downregulates AKT signaling and tumor growth (PMID:26294745); in distinct cellular contexts it selectively routes survival signaling through SGK3 in prostate cancer (PMID:32926495), through RSK2, c-MYC, IRF4, and cyclin Ds in multiple myeloma (PMID:25269480), and directly phosphorylates p70S6K1 in vitro (PMID:39821712). Genetically, PDPK1 lies upstream of GSK3β and mTOR in a branch distinct from AKT-FOXO signaling (PMID:20133737). PDPK1 activity is gated by SUMOylation at K299 by UBC9, which is required for its S241 autophosphorylation and downstream mTORC1 activation, supporting glycolytic metabolism and T-cell proliferation (PMID:35210408, PMID:32876514); deSUMOylation at K296 by SENP3 triggers K48-ubiquitination and proteasomal degradation, suppressing PI3K-AKT signaling (PMID:42140449). PDPK1 also controls autophagy: binding to PIK3C3 (VPS34) inhibits its SUMOylation, and non-SUMOylated PDPK1 tethers LC3 to the ER to initiate autophagosome biogenesis (PMID:32876514), while PDPK1 phosphorylation of SQSTM1/p62 at T138 directs autophagy cargo selection — a mechanism hijacked by coronavirus M protein to shift virophagy toward mitophagy and suppress innate immunity (PMID:39414765). In vivo, vascular endothelial-specific deletion of PDPK1 reduces islet blood flow and beta cell mass and impairs glucose-stimulated insulin secretion (PMID:31055616).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2010 High

    Established that PDPK1 sits upstream of GSK3β and mTOR in a signaling branch genetically separable from AKT, refining its position in the PI3K pathway.

    Evidence Targeted homologous-recombination knockout in human colon cancer lines with downstream signaling readouts, compared against AKT1/AKT2 double knockout

    PMID:20133737

    Open questions at the time
    • Does not identify the direct AKT-independent substrate linking PDPK1 to GSK3β/mTOR
    • Context restricted to colorectal cancer cells
  2. 2011 Medium

    Showed PDPK1 expression is translationally regulated, linking its protein synthesis to the MID1 ubiquitin ligase complex and Opitz syndrome.

    Evidence mRNA co-immunoprecipitation, translational efficiency assays, patient-derived cells, and MID1 rescue

    PMID:21930711

    Open questions at the time
    • MIDAS motif binding mechanism on PDPK1 mRNA not structurally defined
    • Does not establish kinase-pathway consequences of altered PDPK1 levels in patients
  3. 2014 Medium

    Demonstrated PDPK1 drives survival in multiple myeloma by activating a broad set of substrates (RSK2, AKT, c-MYC, IRF4, cyclin Ds), positioning it as a pro-survival therapeutic node.

    Evidence Pharmacological inhibition plus siRNA knockdown with apoptotic and substrate readouts

    PMID:25269480

    Open questions at the time
    • Which substrate phosphorylations are direct versus indirect not resolved
    • Single disease context
  4. 2015 Medium

    Defined the AKT1-PDPK1 physical interaction as required for AKT1 activation and druggable, establishing protein-protein interaction disruption as an anti-tumor strategy.

    Evidence Live-cell PPI inhibitor screen (NSC156529), phospho-AKT westerns, proliferation and xenograft assays

    PMID:26294745

    Open questions at the time
    • Interaction interface not structurally mapped
    • Inhibitor specificity beyond the AKT1-PDPK1 interface not fully excluded
  5. 2017 Medium

    Linked PDPK1 to pathogen-driven metabolic rewiring, showing a PDPK1-MYC-HKII axis prevents apoptosis of Chlamydia-infected cells.

    Evidence Co-IP, imaging, pharmacological inhibition, and HKII-mitochondria blocking peptides in infected cells

    PMID:28803120

    Open questions at the time
    • Whether PDPK1 phosphorylates MYC directly not established
    • Upstream activator of PDPK1 during infection unclear
  6. 2019 Medium

    Revealed PDPK1's autophagy-regulatory role and its control by VPS34 binding, with a viral protein exploiting the PIK3C3-PDPK1 complex to suppress autophagy.

    Evidence Reciprocal co-IP with domain mapping of avibirnavirus VP3, plus autophagy and viral replication assays

    PMID:31885313

    Open questions at the time
    • Direct PIK3C3-PDPK1 binding interface on PDPK1 not mapped
    • Endogenous (non-viral) regulator of complex dissociation unknown
  7. 2019 High

    Provided in vivo evidence that endothelial PDPK1 maintains pancreatic islet vascularity and beta cell function, extending PDPK1 biology to organismal metabolic physiology.

    Evidence Tie2-Cre conditional knockout mice with glucose tolerance, insulin secretion, islet blood flow, IHC, and EM

    PMID:31055616

    Open questions at the time
    • Endothelial substrate of PDPK1 mediating fenestration not identified
    • Cell-autonomous beta cell role not addressed by this model
  8. 2020 Medium

    Identified SUMOylation at K299 as a switch governing PDPK1 autophosphorylation and bifurcating its output between mTOR activation and ER-tethered autophagosome initiation.

    Evidence K299 mutagenesis, in vivo SUMOylation assays, co-IP with PIK3C3, and LC3 localization/fractionation

    PMID:32876514

    Open questions at the time
    • SUMO ligase responsible not identified in this study
    • Structural basis of how K299 SUMOylation enables S241 autophosphorylation unknown
  9. 2020 Medium

    Established SGK3, rather than AKT, as the dominant PDPK1 effector for survival in prostate cancer, demonstrating context-specific substrate selection.

    Evidence shRNA knockdown with constitutively active SGK3 rescue and apoptosis readouts

    PMID:32926495

    Open questions at the time
    • What determines SGK3 versus AKT preference in this context not defined
    • Single cancer type
  10. 2022 Medium

    Assigned the SUMO E2 UBC9 to PDPK1 K299 SUMOylation and connected this modification to immune-cell glycolysis and homeostatic proliferation.

    Evidence K299 mutagenesis, autophosphorylation and mTORC1 assays, and CD4 T-cell proliferation/glycolysis in vivo and in vitro

    PMID:35210408

    Open questions at the time
    • E3 SUMO ligase still not defined
    • Physiological signal triggering UBC9-PDPK1 SUMOylation unknown
  11. 2022 Medium

    Placed PDPK1 in a positive feedback loop with LIFR signaling, where LIFR-S1044 phosphorylation recruits PDPK1 to activate AKT and PDPK1 reinforces LIFR acetylation via GCN5.

    Evidence Mass spectrometry, co-IP, GEM models, and organoids

    PMID:35172032

    Open questions at the time
    • Mechanism by which PDPK1 raises GCN5 levels unclear
    • Direct PDPK1 substrate in the loop not pinpointed
  12. 2024 High

    Showed PDPK1 directs autophagy cargo selection by phosphorylating SQSTM1/p62 at T138, a step coronavirus M protein hijacks to switch virophagy to mitophagy and evade innate immunity.

    Evidence Dual split-fluorescence, T138 mutagenesis, co-IP, peptide inhibitor, and mouse infection model

    PMID:39414765

    Open questions at the time
    • How T138 phosphorylation mechanistically biases cargo recognition not fully resolved
    • Endogenous (non-viral) signals recruiting PDPK1 to p62 unknown
  13. 2024 Medium

    Demonstrated lysosomal-dependent degradation of PDPK1 as a tumor-suppressive route, with AQP3 accumulation inactivating AKT-mTOR and triggering autophagic cell death.

    Evidence FBXW5 knockdown, AQP3 modulation, lysosomal inhibition, and AKT-mTOR/autophagy readouts in HCC cells

    PMID:38726865

    Open questions at the time
    • Direct molecular link between AQP3 and PDPK1 degradation not defined
    • Whether AQP3 binds PDPK1 directly unknown
  14. 2024 Medium

    Showed PDPK1 transcription is driven by SP5, itself controlled by CPT1A-mediated succinylation, connecting metabolic enzyme activity to PDPK1-AKT/mTOR-driven glycolysis.

    Evidence Luciferase reporter, ChIP, co-IP, and Seahorse glycolysis assays in prostate cancer cells

    PMID:38494680

    Open questions at the time
    • Generality of SP5-driven PDPK1 transcription beyond prostate cancer unknown
    • Does not address PDPK1 protein-level regulation
  15. 2024 Low

    Proposed a tripartite N-MYC-WDR5-PDPK1 complex co-regulating mitotic gene expression, extending PDPK1 into transcriptional/chromatin control.

    Evidence RNA-seq, co-IP for N-MYC-PDPK1 interaction, and comparison with WDR5 inhibition data in neuroblastoma

    PMID:38605297

    Open questions at the time
    • Single co-IP without reciprocal/structural validation of the complex
    • No demonstration that PDPK1 kinase activity is required for the gene-regulatory effect
  16. 2025 Medium

    Confirmed by reconstitution that PDPK1 is a direct upstream kinase of p70S6K1 and that this activity does not require its PH domain.

    Evidence Baculovirus co-expression with kinase-Glo and AlphaScreen kinase assays and immunoblotting

    PMID:39821712

    Open questions at the time
    • No active-site mutagenesis to formally exclude indirect activation
    • Phosphosite on p70S6K1 not mapped in this assay
  17. 2026 Medium

    Identified SENP3 as a direct PDPK1 deSUMOylase at K296 that destabilizes PDPK1 via K48-ubiquitination, linking PDPK1 turnover to suppression of PI3K-AKT signaling in intestinal ischemia/reperfusion.

    Evidence IP-mass spectrometry, co-IP, K296 mutagenesis, ubiquitination assays, and SENP3 knockdown

    PMID:42140449

    Open questions at the time
    • E3 ligase mediating the K48-ubiquitination after deSUMOylation not identified
    • Relationship between K296 and K299 SUMO sites not reconciled
  18. 2026 Medium

    Connected PDPK1 to transcriptional anti-apoptotic output via an NFKB1/BIRC3 axis driving radiotherapy resistance.

    Evidence ChIP, dual-luciferase, RNA-seq, siRNA knockdown, and BIRC3 rescue in lung adenocarcinoma

    PMID:41862915

    Open questions at the time
    • Whether PDPK1 activates NFKB1 directly or through an intermediate kinase unclear
    • Single disease context
  19. 2026 Medium

    Established PDPK1 as a druggable target in cuproptosis, where kinase inhibition stabilizes the copper transporter CTR1 and promotes copper-dependent cell death.

    Evidence DARTS drug-binding, kinase activity and ubiquitination assays, organoids, and PDX in colorectal cancer (penfluridol)

    PMID:42185682

    Open questions at the time
    • How AKT1 phosphorylation controls CTR1 ubiquitination mechanistically not resolved
    • Penfluridol off-target effects not fully excluded

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous SUMO E3 ligase and the physiological cues that toggle the K299 SUMOylation / K296 deSUMOylation switch, and how this switch coordinates the bifurcation between mTOR activation and ER-tethered autophagosome biogenesis, remain undefined.
  • No SUMO E3 ligase identified for PDPK1
  • Structural basis coupling SUMOylation to S241 autophosphorylation unknown
  • Reconciliation of K296 versus K299 modification sites needed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 3
Localization
GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 3
Partners
AKT1PIK3C3RPS6KB1RSK2SENP3SGK3SQSTM1WDR5
Complex memberships
N-MYC-WDR5-PDPK1 complexPIK3C3(VPS34)-PDPK1 complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Genetic knockout of PDPK1 in human colorectal cancer cells reduces GSK3β and mTOR activation, whereas AKT1/AKT2 double knockout affects FOXO proteins but not GSK3β or mTOR, placing PDPK1 upstream of GSK3β and mTOR in a pathway distinct from AKT in this context. Targeted homologous recombination knockout in human colon cancer cell lines; downstream signaling assessed by western blot Proceedings of the National Academy of Sciences of the United States of America High 20133737
2014 PDPK1 phosphorylates and activates RSK2, AKT, c-MYC, IRF4, and cyclin Ds in multiple myeloma cells; PDPK1 inhibition induces apoptosis via activation of BIM and BAD. Pharmacological inhibition and siRNA knockdown of PDPK1 in multiple myeloma cell lines; western blot for downstream substrates and apoptotic markers Cancer research Medium 25269480
2017 Chlamydia trachomatis infection activates PDPK1 signaling, which phosphorylates and stabilizes MYC; PDPK1-MYC signaling induces hexokinase II (HKII) expression and HKII translocation/enrichment at mitochondria to prevent apoptosis of infected cells. Biochemical approaches (co-immunoprecipitation, western blot), imaging, pharmacological inhibition of PDPK1 and MYC, exogenous peptides blocking HKII-mitochondria interaction EBioMedicine Medium 28803120
2011 The MID1 ubiquitin ligase complex associates with PDPK1 mRNA via a purine-rich MIDAS sequence motif, increasing its translational efficiency; PDPK1 protein synthesis is significantly reduced in cells from Opitz syndrome patients with mutated MID1 and can be rescued by functional MID1. mRNA co-immunoprecipitation, translational efficiency assays, patient-derived cell comparison, MID1 rescue experiments The Journal of biological chemistry Medium 21930711
2020 PDPK1 SUMOylation at lysine 299 (within the kinase domain) is required for its autophosphorylation at serine 241 and subsequent activation of AKT1-MTOR signaling; SUMOylation of PDPK1 is inhibited by binding to PIK3C3, and non-SUMOylated PDPK1 tethers LC3 to the ER to initiate autophagosome biogenesis. Co-immunoprecipitation, site-directed mutagenesis (K299), in vivo SUMOylation assays, autophagy detection (LC3 localization), biochemical fractionation Autophagy Medium 32876514
2019 Avibirnavirus VP3 CC3 domain disrupts the PIK3C3-PDPK1 complex by directly binding to PIK3C3; release of PDPK1 from PIK3C3 allows PDPK1 to activate the AKT-MTOR pathway, suppressing autophagy to facilitate viral replication. Co-immunoprecipitation, domain mapping, autophagy assays, viral replication assays Autophagy Medium 31885313
2022 UBC9-mediated SUMOylation of PDPK1 at lysine 299 is required for PDPK1 autophosphorylation at serine 241 and downstream mTORC1 activation; loss of PDPK1 SUMOylation impairs CD4 T-cell glycolytic metabolism and homeostatic proliferation. SUMOylation site mutagenesis (K299), autophosphorylation assays, mTORC1 activity assays, T-cell proliferation and glycolysis assays in vivo and in vitro Cell death & disease Medium 35210408
2024 Coronavirus M protein recruits PDPK1 to phosphorylate SQSTM1 (p62) at threonine 138, directing autophagy substrate selection from virophagy toward mitophagy, thereby suppressing innate immunity and promoting viral replication. Dual split-fluorescence assay, site-directed mutagenesis (T138), co-immunoprecipitation, viral replication assays, PDPK1-targeting peptide inhibition, mouse infection model Nature communications High 39414765
2020 PDPK1 mediates prostate cancer cell survival predominantly via phosphorylation and activation of SGK3; PDPK1 knockdown reduces SGK3 phosphorylation, induces apoptosis, and constitutively active SGK3 rescues apoptosis caused by PDPK1 loss, while AKT and SGK1 phosphorylation were not affected. shRNA knockdown, ectopic expression of constitutively active SGK3, western blot for phosphorylation status, apoptosis assays Journal of cellular and molecular medicine Medium 32926495
2015 Physical interaction between AKT1 and PDPK1 is required for AKT1 activation; a small molecule inhibitor (NSC156529) that specifically disrupts the AKT1-PDPK1 interaction downregulates AKT1 signaling, decreases cancer cell proliferation in vitro, and inhibits prostate tumor xenograft growth in vivo. Live cell-based screen for protein-protein interaction inhibitors, western blot for AKT1 phosphorylation, cell proliferation assays, in vivo xenograft model Molecular cancer therapeutics Medium 26294745
2017 ARL15 knockdown specifically inhibits PDPK1 phosphorylation at Ser241, thereby reducing PDPK1 activity and downstream AKT Thr308 phosphorylation in the insulin signaling pathway; ARL15 interacts with ASAP2 (a GAP for ARL15) as identified by co-immunoprecipitation. ARL15 overexpression and knockdown in C2C12 myotubes, western blot for PDPK1-S241 and AKT-T308 phosphorylation, co-immunoprecipitation for ARL15-ASAP2 interaction Biochemical and biophysical research communications Low 28322786
2024 AQP3 accumulation (caused by FBXW5 knockdown) induces lysosomal-dependent degradation of PDPK1, thereby inactivating the AKT-MTOR pathway and inducing autophagic cell death in hepatocellular carcinoma cells. FBXW5 knockdown, AQP3 overexpression/knockdown, lysosomal inhibition, western blot for PDPK1 and AKT-MTOR pathway components, autophagy assays Autophagy Medium 38726865
2022 LIFR-K620 acetylation facilitates LIFR homodimerization and LIFR-S1044 phosphorylation, which recruits PDPK1 to activate AKT signaling; PDPK1 in turn enhances GCN5 protein level, forming a positive feedback loop sustaining LIFR-K620 acetylation. Liquid mass spectrometry, genetically engineered mouse models, organoid assays, co-immunoprecipitation, lentiviral constructs Clinical and translational medicine Medium 35172032
2026 SENP3 directly interacts with PDPK1 (identified by co-immunoprecipitation/mass spectrometry), promotes PDPK1 deSUMOylation at Lys296, leading to increased K48-linked ubiquitination and proteasomal degradation of PDPK1, thereby suppressing PI3K-AKT signaling and inducing apoptosis during intestinal ischemia/reperfusion. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, site-directed mutagenesis (K296), ubiquitination assays, SENP3 knockdown, western blot for PI3K-AKT pathway Biochemical pharmacology Medium 42140449
2024 CPT1A mediates succinylation of SP5, which strengthens SP5 binding to the PDPK1 promoter and activates PDPK1 transcription; elevated PDPK1 then activates AKT/mTOR signaling to promote prostate cancer cell viability and glycolysis. Luciferase reporter assay, ChIP assay, co-immunoprecipitation, CCK-8, Seahorse glycolysis assay Cancer biology & therapy Medium 38494680
2024 N-MYC physically interacts with PDPK1 through the WDR5-PDPK1 interaction in neuroblastoma cells; PDPK1 and N-MYC co-regulate a specific set of genes involved in spindle pole formation and chromosome segregation, overlapping with WDR5-regulated genes, suggesting a tripartite N-MYC-WDR5-PDPK1 complex regulates mitotic gene expression. RNA-seq transcriptomic analysis, co-immunoprecipitation for N-MYC-PDPK1 physical interaction, comparative analysis with WDR5 inhibition data BMC genomics Low 38605297
2019 Vascular endothelial-specific deletion of PDPK1 (Tie2-Cre) reduces islet blood flow, decreases endothelial fenestration, causes hypoxia in islets, and leads to reduced pancreatic beta cell mass and impaired glucose-stimulated insulin secretion, demonstrating a role for endothelial PDPK1 in maintaining islet vascularity and beta cell function. Conditional knockout mice (Tie2+/-/Pdpk1flox/flox), glucose tolerance tests, insulin secretion assays, microsphere islet blood flow measurement, immunohistochemistry, electron microscopy Diabetologia High 31055616
2026 PDPK1 activates NFKB1, which transactivates the anti-apoptotic gene BIRC3; BIRC3 overexpression reverses pro-apoptotic effects of PDPK1 knockdown, establishing PDPK1/NFKB1/BIRC3 as a signaling axis driving radiotherapy resistance in lung adenocarcinoma. ChIP assay, dual-luciferase assay, RNA sequencing, siRNA knockdown, BIRC3 overexpression rescue, colony formation and apoptosis assays Cancer cell international Medium 41862915
2025 PDPK1 co-expressed with RPS6KB1 (p70S6K1) in a baculovirus system phosphorylates and activates p70S6K1, confirming PDPK1 as a direct upstream kinase of p70S6K1; a PH-domain-deleted PDPK1 construct was sufficient for this activity. Baculovirus dual expression system, Kinase-Glo assay, AlphaScreen kinase assay, immunoblotting Molecular biology reports Medium 39821712
2021 In small-cell lung cancer cells, PDPK1 and Akt affect Hedgehog pathway expression (PDPK1 silencing reduces Hedgehog expression), but Hedgehog does not affect PDPK1 or p-Akt expression, placing PDPK1-Akt upstream of Hedgehog signaling. siRNA transfection for PDPK1 and Akt silencing, pharmacological Hedgehog inhibition, proliferation and migration assays, western blot The Journal of international medical research Low 34038205
2026 PDPK1 directly binds penfluridol (demonstrated by drug affinity responsive target stability assay); penfluridol inhibits PDPK1 kinase activity and reduces AKT1 phosphorylation, which decreases CTR1 ubiquitination, stabilizes CTR1 on the plasma membrane, and promotes intracellular copper accumulation leading to cuproptosis in colorectal cancer. Drug affinity responsive target stability (DARTS) assay, PDPK1 kinase activity assay, ubiquitination assay, western blot for p-AKT1 and CTR1, patient-derived organoids, PDX model Acta pharmacologica Sinica Medium 42185682

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proceedings of the National Academy of Sciences of the United States of America 115 20133737
2018 Circular RNA hsa_circ_0004015 regulates the proliferation, invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway. Biochemical and biophysical research communications 109 30509491
2021 POU2F2 regulates glycolytic reprogramming and glioblastoma progression via PDPK1-dependent activation of PI3K/AKT/mTOR pathway. Cell death & disease 60 33931589
2020 Interleukin 1β-mediated HOXC10 Overexpression Promotes Hepatocellular Carcinoma Metastasis by Upregulating PDPK1 and VASP. Theranostics 53 32206125
2020 LncRNA KTN1-AS1 promotes the progression of non-small cell lung cancer via sponging of miR-130a-5p and activation of PDPK1. Oncogene 49 32820252
2020 FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke. Translational stroke research 42 32036560
2017 Chlamydia trachomatis Prevents Apoptosis Via Activation of PDPK1-MYC and Enhanced Mitochondrial Binding of Hexokinase II. EBioMedicine 40 28803120
2012 The 16p13.3 (PDPK1) Genomic Gain in Prostate Cancer: A Potential Role in Disease Progression. Translational oncology 34 23401739
2021 Rosmarinic Acid Regulates Microglial M1/M2 Polarization via the PDPK1/Akt/HIF Pathway Under Conditions of Neuroinflammation. Inflammation 33 32940818
2014 Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma. Cancer research 32 25269480
2019 Binding of Avibirnavirus VP3 to the PIK3C3-PDPK1 complex inhibits autophagy by activating the AKT-MTOR pathway. Autophagy 31 31885313
2011 Protein phosphatase 2A (PP2A)-specific ubiquitin ligase MID1 is a sequence-dependent regulator of translation efficiency controlling 3-phosphoinositide-dependent protein kinase-1 (PDPK-1). The Journal of biological chemistry 27 21930711
2020 LncRNA CAR10 Upregulates PDPK1 to Promote Cervical Cancer Development by Sponging miR-125b-5p. BioMed research international 26 32025520
2020 PDPK1 regulates autophagosome biogenesis by binding to PIK3C3. Autophagy 26 32876514
2020 Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival. Journal of cellular and molecular medicine 25 32926495
2018 A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay. Genetics in medicine : official journal of the American College of Medical Genetics 25 30245510
2017 Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma. British journal of haematology 24 28439875
2022 A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma. Cancer research 23 35657206
2024 CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells. Cancer biology & therapy 20 38494680
2020 Long non-coding RNA ABHD11-AS1 boosts gastric cancer development by regulating miR-361-3p/PDPK1 signalling. Journal of biochemistry 20 32678870
2022 SUMOylation of PDPK1 Is required to maintain glycolysis-dependent CD4 T-cell homeostasis. Cell death & disease 19 35210408
2019 Vascular endothelial PDPK1 plays a pivotal role in the maintenance of pancreatic beta cell mass and function in adult male mice. Diabetologia 19 31055616
2018 Loss of PDPK1 abrogates resistance to gemcitabine in label-retaining pancreatic cancer cells. BMC cancer 18 30064387
2018 miR-718 is involved in malignancy of papillary thyroid cancer through repression of PDPK1. Pathology, research and practice 16 30166214
2017 ADP-ribosylation factor-like GTPase 15 enhances insulin-induced AKT phosphorylation in the IR/IRS1/AKT pathway by interacting with ASAP2 and regulating PDPK1 activity. Biochemical and biophysical research communications 16 28322786
2024 SCFFBXW5-mediated degradation of AQP3 suppresses autophagic cell death through the PDPK1-AKT-MTOR axis in hepatocellular carcinoma cells. Autophagy 15 38726865
2022 Leukemia inhibitory factor receptor homodimerization mediated by acetylation of extracellular lysine promotes prostate cancer progression through the PDPK1/AKT/GCN5 axis. Clinical and translational medicine 15 35172032
2022 Downregulating PDPK1 and taking phillyrin as PDPK1-targeting drug protect hepatocytes from alcoholic steatohepatitis by promoting autophagy. Cell death & disease 14 36418288
2023 Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model. The American journal of Chinese medicine 12 37530505
2015 A Novel Inhibitor of AKT1-PDPK1 Interaction Efficiently Suppresses the Activity of AKT Pathway and Restricts Tumor Growth In Vivo. Molecular cancer therapeutics 12 26294745
2023 Extracellular vesicle-derived circCEBPZOS attenuates postmyocardial infarction remodeling by promoting angiogenesis via the miR-1178-3p/PDPK1 axis. Communications biology 11 36726025
2021 CircRNA ANXA2 Promotes Lung Cancer Proliferation and Metastasis by Upregulating PDPK1 Expression. Journal of oncology 11 34992655
2024 circRNA-CPA4 Regulates Cell Proliferation and Apoptosis of Non-small Cell Lung Cancer via the miR-1183/PDPK1 Axis. Biochemical genetics 10 38273153
2023 Activation of long-non-coding RNA NEAT1 sponging microRNA-147 inhibits radiation damage by targeting PDPK1 in troxerutin radioprotection. iScience 9 36698722
2020 gga-miR-148a-5p-Targeting PDPK1 Inhibits Proliferation and Cell Cycle Progression of Avain Leukosis Virus Subgroup J (ALV-J)-Infected Cells. Frontiers in cell and developmental biology 9 33384993
2019 CT-707 Overcomes Resistance of Crizotinib through Activating PDPK1- AKT1 Pathway by Targeting FAK. Current cancer drug targets 9 30381078
2024 Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138. Nature communications 8 39414765
2023 circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway. Open medicine (Warsaw, Poland) 8 36820067
2022 Identification of 11-Hydroxytephrosin and Torosaflavone A as Potential Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1): Toward Anticancer Drug Discovery. Biology 7 36009858
2021 Mini-Review: PDPK1 (3-phosphoinositide dependent protein kinase-1), An Emerging Cancer Stem Cell Target. Journal of cancer treatment & diagnosis 7 34079928
2019 miR‑16‑2‑3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in maxillary primordium mesenchymal cells. International journal of molecular medicine 7 30664182
2024 Remimazolam attenuates inflammation in bronchopneumonia through the inhibition of NLRP3 activity by PDPK1 ubiquitination. Chemical biology & drug design 6 38230783
2025 PDPK1 governs macrophage M2 polarization via hypoxia-driven CD47/AKT-glycolytic Axis in endometriosis. Cellular signalling 5 40480430
2023 Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B-cell lymphomas. Cancer science 5 37840379
2018 A new and important relationship between miRNA-147a and PDPK1 in radiotherapy. Journal of cellular biochemistry 5 29144017
2016 The inhibition of Akt-Pdpk1 interaction efficiently suppresses the growth of murine primary liver tumor cells. Biochemical and biophysical research communications 5 27103434
2024 Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470 Synergistically Inhibit Renal Cell Carcinoma Pathogenesis. Journal of Cancer 4 38356720
2021 Possible involvement of the Hedgehog and PDPK1-Akt pathways in the growth and migration of small-cell lung cancer. The Journal of international medical research 4 34038205
2025 Circ_0084927 promotes progression of intrahepatic cholangiocarcinoma by sponging miR-4725-5p to activate the PDPK1/AKT/mTOR signaling pathway. Cellular signalling 2 40581264
2024 In Vitro and Vivo Experiments Revealing Astragalin Inhibited Lung Adenocarcinoma Development via LINC00582/miR-140-3P/PDPK1. Journal of biochemical and molecular toxicology 2 39552470
2024 Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer. Heliyon 2 39624293
2019 Correction to: Vascular endothelial PDPK1 plays a pivotal role in the maintenance of pancreatic beta cell mass and function in adult male mice. Diabetologia 2 31605154
2026 Acetylcholine enhances HIF-1α signaling in pancreatic cancer cells under hypoxia through the nAChR-α7/PDPK1/YAP pathway. International journal of biological sciences 1 41608625
2024 Mitotic gene regulation by the N-MYC-WDR5-PDPK1 nexus. BMC genomics 1 38605297
2026 MicroRNA-374b-5p suppresses osteosarcoma progression via the PDPK1-mediated AKT pathway. Translational cancer research 0 41674951
2026 PDPK1 activates BIRC3 via NFKB1 to promote radiotherapy resistance in lung adenocarcinoma. Cancer cell international 0 41862915
2026 SENP3 promotes PDPK1 deSUMOylation to inhibit the PI3K-Akt signaling pathway and induce apoptosis in intestinal ischemia/reperfusion. Biochemical pharmacology 0 42140449
2026 Penfluridol directly targets PDPK1 to suppress AKT1 phosphorylation and stabilize CTR1, inducing cuproptosis in colorectal cancer. Acta pharmacologica Sinica 0 42185682
2025 Co-expression of the RPS6KB1 and PDPK1 genes for production of activated p70S6K1 using bac-to-bac baculovirus expression system. Molecular biology reports 0 39821712
2025 Mechanistic role of miR-375 in regulating PDPK1 to promote progression of small bowel neuroendocrine tumors: a silico analysis. Discover oncology 0 40549235
2025 CircGLIS3 Regulates the Proliferation and Apoptosis of Bovine Intramuscular Preadipocytes via the miR-21-3p/PDPK1/AKT Axis. Journal of agricultural and food chemistry 0 41447647

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