Affinage

TPD52

Tumor protein D52 · UniProt P55327

Length
224 aa
Mass
24.3 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPD52 is a coiled-coil adaptor protein that couples Ca2+-regulated membrane trafficking to secretory, autophagic, and metabolic programs, and whose overexpression drives oncogenic transformation (PMID:17314271, PMID:20032513). Through its coiled-coil motif—necessary but not sufficient, with C-terminal regions stabilizing binding—it homo- and heterodimerizes with other TPD52-family members and engages heterologous partners including the apical-transport proteolipid MAL2 (PMID:9484778, PMID:11594751, PMID:11549320). Its trafficking activity is gated by Ca2+-dependent phosphorylation at S136, catalyzed by CAMK2delta6; phosphomimetic S136E constitutively drives LAMP1 to the plasma membrane while S136A abolishes Ca2+-stimulated LAMP1 accumulation, and TPD52 co-localizes with AP-3, Rab27A, VAMP7 and LAMP1 in lysosome-like secretory organelles (PMID:18832449, PMID:20032513). This same S136-dependent endomembrane trafficking is required for midbody vesicle delivery during cytokinesis and for apical endolysosomal secretion of LAMP1 and amylase in pancreatic acinar cells (PMID:20946871, PMID:23868405). TPD52 also localizes to the Golgi/TGN and is delivered to lipid droplets in a microtubule-dependent manner, where it promotes triglyceride synthesis and droplet formation through direct interaction with ADRP/PLIN2 (PMID:26183179, PMID:31278300). Beyond trafficking, TPD52 acts as a regulatory hub: it directly binds HSPA8/HSC70 to enhance chaperone-mediated autophagy—an interaction disrupted by KAT2B-mediated K163 acetylation that HDAC2 reverses (PMID:34034634)—binds PRDX1 to boost peroxidase activity and oxidative-stress handling (PMID:30981892), and negatively regulates ATM protein levels and AMPK/LKB1 signaling (PMID:23974097, PMID:35666017, PMID:37040029). In cancer cells TPD52 promotes proliferation, migration via αvβ3 integrin/Akt, NF-κB–STAT3-driven invasion and EMT, and resistance to mitochondrial apoptosis (PMID:18959755, PMID:28466782), while its abundance is controlled by APC/C-Cdc20-mediated ubiquitination and its mRNA stabilized by TIA-1/TIAR binding to the 3'-UTR (PMID:39401430, PMID:28298474).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Established the structural basis of TPD52 oligomerization, showing the family self-associates through predicted coiled-coil domains—the founding mechanistic feature of these proteins.

    Evidence Reciprocal yeast two-hybrid and GST pull-down across paired family constructs from a breast carcinoma library

    PMID:9484778

    Open questions at the time
    • No heterologous partners identified
    • No functional consequence of dimerization established
    • No structure of the coiled-coil interface
  2. 2001 High

    Refined the interaction determinants and identified the first non-family partner, showing the coiled-coil is necessary but not sufficient and that TPD52 binds the apical-transport proteolipid MAL2, linking it to membrane trafficking.

    Evidence Yeast two-hybrid plus GST pull-down with C-terminal deletion mapping; MAL2 screen confirmed with in vitro translated protein

    PMID:11549320 PMID:11594751

    Open questions at the time
    • Functional role of MAL2 binding not demonstrated
    • Cellular trafficking step not defined
  3. 2004 Medium

    Connected TPD52 to regulated secretion, showing Ca2+-dependent binding to annexin VI in plasma cells.

    Evidence Co-immunoprecipitation in Thiel myeloma cells with MS identification

    PMID:15576473

    Open questions at the time
    • Single co-IP without reciprocal validation
    • Secretory function inferred, not directly tested
  4. 2008 High

    Defined the regulatory switch on TPD52, pinpointing S136 as the single major Ca2+-dependent phospho-acceptor and CAMK2delta6 as the responsible kinase.

    Evidence Mass spectrometry, site-directed mutagenesis, phospho-specific antibody, in-gel kinase assay, and pharmacological inhibition (KN93, W7)

    PMID:18832449

    Open questions at the time
    • Downstream effect of phosphorylation not yet shown
    • Direct kinase-substrate reconstitution not performed
  5. 2009 High

    Assigned a function to S136 phosphorylation, showing it controls Ca2+-stimulated trafficking of LAMP1 to the plasma membrane via lysosome-like secretory organelles.

    Evidence Phosphomutant reconstitution (S136E/S136A), cell-surface labeling, and co-localization with AP-3/Rab27A/VAMP7/LAMP1 across CHO-K1, NRK, HeLa

    PMID:20032513

    Open questions at the time
    • Molecular machinery linking TPD52 to the docking/fusion step unresolved
    • Direct cargo-selection mechanism unknown
  6. 2010 High

    Extended the trafficking role to cell division, showing S136-dependent endomembrane delivery to the midbody is required for cytokinesis.

    Evidence Phosphomutant expression with electron microscopy, VAMP8 co-localization, and multinucleation quantification

    PMID:20946871

    Open questions at the time
    • Precise abscission step affected not defined
    • Relationship to other midbody trafficking factors unknown
  7. 2013 Medium

    Demonstrated a physiological secretory role and a separate DNA-damage-related function: TPD52 drives apical endolysosomal secretion in acinar cells and acts as a negative regulator of ATM protein levels.

    Evidence Adenoviral gain-of-function with S136 mutagenesis and amylase/LAMP1 secretion assays; GST pull-down, reciprocal co-IP, domain mapping, and clonogenic radiation assays

    PMID:23868405 PMID:23974097

    Open questions at the time
    • Mechanism of ATM downregulation (degradation route) not defined
    • ATM finding from a single lab
  8. 2015 High

    Identified a lipid-metabolic function, showing TPD52 promotes triglyceride synthesis and lipid droplet formation through direct, isoform-specific binding to ADRP/PLIN2 at the Golgi.

    Evidence Stable expression, fatty acid incorporation, subcellular fractionation, yeast two-hybrid, and GST pull-down in 3T3 cells

    PMID:26183179

    Open questions at the time
    • Enzymatic step in triglyceride synthesis affected unknown
    • Physiological relevance in vivo not tested here
  9. 2014 Medium

    Expanded the interactome with PLP2 and RAB5C binding to a region distinct from the coiled-coil, reinforcing an endosomal-trafficking role.

    Evidence Yeast two-hybrid screen, GST pull-down, and interaction domain mapping

    PMID:24604726

    Open questions at the time
    • Functional consequence of PLP2/RAB5C binding not shown
    • Single lab
  10. 2016 Medium

    Linked a specific TPD52 isoform to prostate cancer phenotype, showing isoform 1 (PC-1) drives IL-6-enhanced neuroendocrine transdifferentiation.

    Evidence Inducible overexpression with NE marker immunostaining and IL-6 treatment in LNCaP

    PMID:26846108

    Open questions at the time
    • Mechanism connecting PC-1 to NE program unknown
    • Isoform-specific partners not identified
  11. 2017 Medium

    Established post-transcriptional control and an oncogenic signaling axis: TIA-1/TIAR stabilize TPD52 mRNA via the 3'-UTR, while TPD52 binds NF-κB p65 to drive STAT3 cross-talk, invasion, and EMT.

    Evidence RIP, biotin pull-down, 3'-UTR reporter and mRNA-stability assays; co-IP with NF-κB p65 plus MMP-9/EMT readouts in LNCaP

    PMID:28298474 PMID:28466782

    Open questions at the time
    • Direct vs indirect NF-κB binding not fully resolved
    • Growth-factor regulation of TIA-1/TIAR binding mechanism partial
  12. 2019 High

    Defined oxidative-stress and trafficking-route mechanisms: TPD52 binds PRDX1 at its C-terminal PEST domain to enhance peroxidase activity, and reaches lipid droplets via a microtubule-dependent TGN route.

    Evidence TAP, GST pull-down, co-IP, domain mapping and peroxidase/dimerization assays; BFA time-course, nocodazole, and N-terminal deletion mutant localization

    PMID:30981892 PMID:31278300

    Open questions at the time
    • How TPD52 enhances PRDX1 catalysis structurally unknown
    • TGN-to-LD transfer machinery not identified
  13. 2021 High

    Connected TPD52 to autophagy regulation by two routes: direct HSPA8 binding enhances chaperone-mediated autophagy under acetylation control (KAT2B/HDAC2 at K163), and hypoxia-stabilized TPD52 inhibits autophagy by lowering p62.

    Evidence Co-IP, in vitro acetylation, K163 mutagenesis and xenografts; hypoxia mRNA-stability and HIF-epistasis assays with TIA-1/TIAR binding

    PMID:34034634 PMID:34217360

    Open questions at the time
    • Apparent dual autophagy roles (CMA-enhancing vs autophagy-inhibiting) not reconciled
    • Substrate selectivity of TPD52-HSPA8 CMA not defined
  14. 2022 High

    Identified TPD52 as a direct negative regulator of energy-stress AMPK signaling, with metabolic consequences in vivo.

    Evidence TAP-MS, co-IP, in vitro kinase assay, and TPD52 transgenic mice with metabolic phenotyping

    PMID:35666017

    Open questions at the time
    • Mechanism by which binding inhibits AMPKα catalysis unclear
    • Relationship to LKB1 axis not integrated here
  15. 2023 Medium

    Refined the AMPK axis upstream, showing TPD52 binds LKB1 to suppress LKB1 autophosphorylation and AMPK activation, with AMPK reciprocally downregulating TPD52 via GSK3β.

    Evidence Co-IP, MD simulation, AICAR and LiCl pharmacology, and pLKB1/pAMPK immunoblotting in prostate cancer cells

    PMID:37040029

    Open questions at the time
    • Direct LKB1 kinase inhibition not demonstrated in vitro
    • Single lab; computational interaction model unconfirmed structurally
  16. 2024 Medium

    Revealed a context-dependent tumor-suppressor role and degradation pathway: TPD52 promotes S2P-mediated ATF6 cleavage to couple ER stress/UPR to chaperone machinery, and is targeted for proteolysis by APC/C-Cdc20.

    Evidence Co-IP (ATF6, Cdc20), ubiquitination assays, UPR signaling, rescue experiments, and in vivo tumor models in bladder cancer

    PMID:39401430

    Open questions at the time
    • Tumor-suppressor vs oncogenic role reconciliation across tissues unresolved
    • Cdc20 degron on TPD52 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TPD52's many partner interactions and post-translational controls are integrated into a single coherent regulatory logic—and what determines its opposing oncogenic versus tumor-suppressive outputs across tissues—remains unresolved.
  • No structural model of any TPD52 complex
  • Determinants of tissue-specific tumor-suppressor vs oncogene behavior unknown
  • Interplay among S136 phosphorylation, K163 acetylation, and Cdc20 ubiquitination not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0008289 lipid binding 2
Localization
GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 2 GO:0005811 lipid droplet 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 2
Partners
ANXA6ATMHSPA8MAL2PLIN2PLP2PRDX1RAB5C

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TPD52-like proteins interact in homo- and heteromeric fashions through their predicted coiled-coil domains, as demonstrated by yeast two-hybrid co-transfection and GST pull-down assays. Two-hybrid screening of a human breast carcinoma library identified hD53 and hD52 as interactors for both hD52 and hD53 baits. Yeast two-hybrid system and GST pull-down assays Oncogene High 9484778
2001 The coiled-coil motif of TPD52 is necessary but not sufficient for interactions with other D52-like proteins; C-terminal regions facilitate and/or stabilize these interactions, as shown by analysis of C-terminally deleted D52 proteins in yeast two-hybrid and pull-down assays. Yeast two-hybrid system and GST pull-down assays with deletion mutants Biochemical and biophysical research communications Medium 11594751
2001 TPD52 physically interacts with MAL2, a novel four-transmembrane proteolipid protein involved in apical vesicle transport, identifying MAL2 as the first heterologous binding partner of TPD52-like proteins. MAL2 bound all TPD52-like baits in yeast two-hybrid, and in vitro translated MAL2 specifically bound GST-Tpd52 in pull-down assays. Yeast two-hybrid screen and GST pull-down assay with in vitro translated MAL2 Genomics High 11549320
2004 TPD52 binds annexin VI in a Ca2+-dependent manner in the Thiel myeloma cell line, suggesting these molecules may act together to regulate secretory processes in plasma cells, as demonstrated by co-immunoprecipitation. Co-immunoprecipitation in Thiel myeloma cells; 2D-PAGE/mass spectrometry protein identification Blood Medium 15576473
2008 Ca2+-dependent phosphorylation of TPD52 occurs at serine residue 136 (S136), mediated by CAMK2delta6. Mass spectrometry and site-directed mutagenesis identified S136 as the single major phospho-acceptor site, and a specific CAMK2 isoform (CAMK2delta6) co-migrated and co-localized with TPD52, with phosphorylation inhibited by KN93 and calmodulin antagonist W7. Mass spectrometry, site-directed mutagenesis, phospho-specific antibody, in-gel kinase assay, co-localization, pharmacological inhibitors American journal of physiology. Gastrointestinal and liver physiology High 18832449
2009 Ca2+-dependent phosphorylation of TPD52 at S136 modulates trafficking of lysosomal membrane protein LAMP1 to the plasma membrane. Phosphomimetic mutants (S136E) constitutively induced LAMP1 plasma membrane accumulation independent of Ca2+, while the phospho-null mutant (S136A) abolished Ca2+-stimulated LAMP1 accumulation. TPD52 co-localized with AP-3, Rab27A, VAMP7, and LAMP1 in lysosome-like secretory organelles. Site-specific mutagenesis, immunofluorescence co-localization, cell surface antibody labeling, live-cell Ca2+ stimulation assays in CHO-K1, NRK, and HeLa cells American journal of physiology. Cell physiology High 20032513
2010 TPD52 expression and phosphorylation at S136 play a role in cytokinesis via endomembrane trafficking. Ectopic expression of the phospho-null S136A mutant caused a 9-fold increase in multinucleated cells. TPD52 co-localized with VAMP8-positive vesicular structures at the cell midbody, and this co-localization increased with elevated Ca2+. Expression of phosphomutants (S136A, S136E), electron microscopy, immunofluorescence co-localization with VAMP8, multinucleation quantification Biochemical and biophysical research communications High 20946871
2013 TPD52 regulates apical endolysosomal secretion in pancreatic acinar cells. Adenoviral restoration of D52 levels in cultured acinar cells rescued levels of endolysosomal proteins (EEA1, Rab5, LAMP1) and strongly enhanced secretion of both LAMP1 (endolysosomal pathway) and amylase. Secretory effects were absent with alanine substitution at S136 (the major D52 phosphorylation site) and inhibited by brefeldin A. Adenoviral D52 delivery to isolated acinar cells, S136 site-directed mutagenesis, cell-surface antigen labeling of LAMP1, amylase secretion assays, brefeldin A inhibition American journal of physiology. Gastrointestinal and liver physiology High 23868405
2013 TPD52 directly interacts with ATM kinase and acts as a negative regulator of ATM protein levels. Increased TPD52 expression downregulated steady-state ATM protein (but not mRNA), compromised ATM-mediated DNA damage responses following gamma irradiation, and increased radiation sensitivity. Interaction domains were mapped to TPD52 residues 111–131 and ATM residues 1–245 and 772–1102. GST pull-down and co-immunoprecipitation assays, domain mapping, clonogenic radiation assays, immunoblotting in breast cancer and 3T3 cells Cell cycle (Georgetown, Tex.) Medium 23974097
2015 TPD52 expression increases neutral lipid storage in cultured cells by promoting fatty acid incorporation into triglyceride and increasing lipid droplet numbers. TPD52 co-localizes with Golgi (but not ER) markers and partially with ADRP-coated lipid droplets. Direct interaction between ADRP (PLIN2) and TPD52, but not TPD52L1, was demonstrated by yeast two-hybrid and confirmed by GST pull-down. Stable expression in 3T3 cells, lipid droplet quantification, fatty acid incorporation assays, subcellular fractionation, immunofluorescence co-localization, yeast two-hybrid, GST pull-down Journal of cell science High 26183179
2014 TPD52 interacts with PLP2 and RAB5C as novel binding partners, identified by large yeast two-hybrid screen and confirmed by GST pull-down assays. Interaction domain mapping indicated that both proteins interact with a novel binding region of TPD52 distinct from the coiled-coil domain. Yeast two-hybrid screen, GST pull-down assays, interaction domain mapping Molecular biology reports Medium 24604726
2017 TPD52 post-transcriptional regulation is mediated by RNA-binding proteins TIA-1 and TIAR, which bind to the 78–280 region of the TPD52 mRNA 3'-UTR to stabilize the transcript. Knockdown of TIA-1/TIAR decreased TPD52 mRNA stability and expression. TGF-β and EGF stimulation decreased TIA-1/TIAR binding to TPD52 mRNA, resulting in decreased mRNA stability. RNA immunoprecipitation (RIP), biotin pull-down, mRNA degradation assays, 3'-UTR deletion reporter constructs, siRNA knockdown of TIA-1/TIAR The Biochemical journal High 28298474
2008 TPD52 knockdown in LNCaP prostate cancer cells induces apoptosis involving caspase-3 and caspase-9 activation and loss of mitochondrial membrane potential, placing TPD52 function upstream of the mitochondrial apoptotic pathway. Overexpression of TPD52 increased proliferation and promoted cell migration via αvβ3 integrin through activation of the PKB/Akt signaling pathway. shRNA knockdown and EGFP-TPD52 overexpression in LNCaP cells, caspase activity assays, mitochondrial membrane potential measurement, migration assays, integrin blocking The FEBS journal Medium 18959755
2007 Expression of murine TPD52 (mD52) in BALB/c 3T3 fibroblasts induced cellular transformation, anchorage-independent growth, tumorigenesis in immunocompetent mice, and spontaneous lung metastasis. TGF-βR1 expression decreased and TGF-β1 secretion increased in mD52-expressing cells, suggesting TGF-β pathway involvement in mD52-induced metastasis. Stable transfection of 3T3 cells with mD52 cDNA, in vitro growth assays, syngeneic subcutaneous tumor challenge, lung nodule quantification, cDNA microarray, TGF-β pathway analysis Molecular cancer research : MCR High 17314271
2008 D52 overexpression in BALB/c 3T3 cells (but not D53 overexpression) confers increased proliferation and anchorage-independent growth capacity, while D52 knockdown (but not D53) in SK-BR-3 cells significantly increases apoptosis, demonstrating non-redundant and isoform-specific functions for D52 versus its paralogs. Stable expression in BALB/c 3T3 fibroblasts, transient siRNA knockdown in breast carcinoma cell lines, proliferation and soft agar assays, apoptosis assays Clinical cancer research Medium 18698023
2017 TPD52 (isoform 3) directly interacts with NF-κB p65 (RelA) and promotes accumulation of phosphorylated NF-κB (p65)S536, transactivating NF-κB target genes. TPD52 also activates STAT3 through an NF-κB–STAT3 cross-talk. TPD52 promotes invasion via increased MMP-9 expression and promotes EMT by inducing loss of E-cadherin and expression of vimentin and VCAM, as well as activation of focal adhesion kinase. Co-immunoprecipitation (TPD52–NF-κB p65), overexpression and shRNA knockdown of TPD52 in LNCaP cells, NF-κB inhibition, cytokine secretion assays, MMP activity assays, Western blotting Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine Medium 28466782
2019 TPD52 (isoform 3) interacts with Peroxiredoxin 1 (PRDX1) at the C-terminal PEST domain (residues 152–179) of TPD52, and this interaction increases PRDX1 peroxidase activity and promotes PRDX1 dimerization. H2O2 exposure evoked increased TPD52–PRDX1 interaction. Depletion of both proteins led to H2O2 accumulation, linking TPD52 to oxidative stress management in prostate cancer cells. GST pull-down, tandem affinity purification, co-immunoprecipitation, interaction domain mapping, peroxidase activity assays, dimerization assays, H2O2 measurement Biochimica et biophysica acta. Molecular cell research High 30981892
2021 TPD52 enhances chaperone-mediated autophagy (CMA) activation by directly interacting with HSPA8/HSC70 and enhancing substrate degradation in prostate cancer cells. TPD52 is acetylated by KAT2B at K163; this acetylation is reversed by HDAC2. Acetylation of TPD52 at K163 compromises the TPD52–HSPA8 interaction, leading to impaired CMA function and reduced tumor growth in vivo. Co-immunoprecipitation (TPD52–HSPA8), CMA activity assays, in vitro acetylation assay (KAT2B), HDAC2 inhibition, K163 mutagenesis, xenograft tumor models Autophagy High 34034634
2022 TPD52 directly interacts with AMPKα and inhibits AMPKα kinase activity in vitro and in vivo. TPD52 transgenic mice showed AMPK inhibition and multiple metabolic defects, identifying TPD52 as a novel negative regulator of energy stress-induced AMPK activation. Tandem affinity purification/mass spectrometry to identify AMPKα as TPD52-interacting protein, co-immunoprecipitation, in vitro kinase assay, TPD52 transgenic mice with metabolic phenotyping Cancer medicine High 35666017
2023 TPD52 (isoform 3) interacts with LKB1 (serine/threonine kinase 11), and this interaction suppresses LKB1 auto-phosphorylation and consequently inhibits AMPK activation (reducing pLKB1-Ser428 and pAMPK-Thr172). AMPK activation by AICAR downregulated TPD52 via GSK3β, inhibiting PCa cell proliferation and migration. Co-immunoprecipitation, molecular modeling and MD simulations (interaction domain), AICAR treatment, GSK3β inhibition (LiCl), Western blotting for pLKB1 and pAMPK Journal of cell communication and signaling Medium 37040029
2024 TPD52 functions as a tumor suppressor in bladder cancer by promoting S2P-mediated cleavage of ATF6 to integrate ER stress and UPR signaling with the chaperone machinery. The APC/C-Cdc20 E3 ligase mediates polyubiquitination and proteolysis of TPD52, and Cdc20 inactivation sensitized cancer cells to ER stress inducers in a TPD52-dependent manner. Co-immunoprecipitation (TPD52–ATF6, TPD52–Cdc20), ubiquitination assays, ER stress/UPR signaling assays, loss-of-function and rescue experiments, in vivo tumor models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39401430
2019 Delayed recruitment of TPD52 to lipid droplets (LDs) occurs via the Golgi/trans-Golgi network (TGN) and is microtubule-dependent. After Brefeldin A treatment, TPD52 first co-localizes with TGN marker syntaxin 6 (1–3 hours) before moving to LDs (5 hours), and this shift is disrupted by nocodazole (microtubule depolymerizer). An N-terminally deleted TPD52 mutant (residues 40–184) constitutively targeted to LDs regardless of treatment. Immunofluorescence co-localization (BFA treatment time course), nocodazole treatment, N-terminal deletion mutant expression, LD quantification in 3T3 and breast cancer cell lines Scientific reports Medium 31278300
2016 TPD52 isoform 1 (PC-1) promotes neuroendocrine (NE) transdifferentiation of LNCaP prostate cancer cells. Overexpression of PC-1 alone initiates NE characteristics; IL-6 treatment markedly enhanced this effect and significantly upregulated PC-1 (but not other TPD52 isoforms). Immunofluorescence showed PC-1 accumulation at the ends of neuron-like cell processes in NE-differentiated cells. Inducible overexpression system (LNCaP), IL-6 treatment, NE marker immunostaining (chromogranin A, synaptophysin, β-3 tubulin), immunofluorescence localization, AR status analysis Tumour biology Medium 26846108
2021 Under hypoxic conditions in oral squamous cell carcinoma cells, TPD52 mRNA is stabilized by binding of T-cell intercellular antigen 1 (TIA-1) and TIA-related protein (TIAR) to TPD52 mRNA, upregulating TPD52 expression in a HIF-independent manner. In vivo, TPD52 acted as an autophagy inhibitor by reducing p62 levels. qRT-PCR, Western blotting under hypoxia, HIF inhibition, mRNA stability assays, RBP–mRNA binding (TIA-1/TIAR), RNAi knockdown, xenograft experiments Cell & bioscience Medium 34217360
1998 Alternative splicing within the D52 gene family alters the protein-protein interaction capabilities of encoded isoforms. A truncated hD53 isoform displayed altered interaction capabilities in the yeast two-hybrid system compared to full-length hD53, demonstrating functional consequences of alternative splicing. Yeast two-hybrid interaction analysis of alternatively spliced isoforms Biochimica et biophysica acta Low 9838088

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Overexpression, amplification, and androgen regulation of TPD52 in prostate cancer. Cancer research 147 15172988
2004 PrLZ, a novel prostate-specific and androgen-responsive gene of the TPD52 family, amplified in chromosome 8q21.1 and overexpressed in human prostate cancer. Cancer research 96 14996714
1996 Definition of the tumor protein D52 (TPD52) gene family through cloning of D52 homologues in human (hD53) and mouse (mD52). Genomics 86 8812487
2005 Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer. International journal of cancer 81 15986428
2001 Identification of MAL2, a novel member of the mal proteolipid family, though interactions with TPD52-like proteins in the yeast two-hybrid system. Genomics 80 11549320
2000 The hD52 (TPD52) gene is a candidate target gene for events resulting in increased 8q21 copy number in human breast carcinoma. Genes, chromosomes & cancer 79 10918393
2008 Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer. Clinical biochemistry 78 18710659
2008 Altered expression of tumor protein D52 regulates apoptosis and migration of prostate cancer cells. The FEBS journal 71 18959755
2004 The tumor protein D52 family: many pieces, many puzzles. Biochemical and biophysical research communications 71 15555543
1998 Identification of homo- and heteromeric interactions between members of the breast carcinoma-associated D52 protein family using the yeast two-hybrid system. Oncogene 71 9484778
2014 Tumour-suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer. FEBS letters 63 24768995
2014 Tumor protein D52 (TPD52) and cancer-oncogene understudy or understudied oncogene? Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 58 24798974
2010 MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome. BMC cancer 56 20846453
2021 Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis. Drug design, development and therapy 55 33976535
2014 microRNA-218 inhibits prostate cancer cell growth and promotes apoptosis by repressing TPD52 expression. Biochemical and biophysical research communications 54 25511701
2008 Nonredundant functions for tumor protein D52-like proteins support specific targeting of TPD52. Clinical cancer research : an official journal of the American Association for Cancer Research 54 18698023
2007 Induction of tumorigenesis and metastasis by the murine orthologue of tumor protein D52. Molecular cancer research : MCR 54 17314271
2016 Regulation of TPD52 by antitumor microRNA-218 suppresses cancer cell migration and invasion in lung squamous cell carcinoma. International journal of oncology 50 27633630
1998 Cloning of a third member of the D52 gene family indicates alternative coding sequence usage in D52-like transcripts. Biochimica et biophysica acta 44 9838088
2020 Knockdown of lncRNA PCAT6 Enhances Radiosensitivity in Triple-Negative Breast Cancer Cells by Regulating miR-185-5p/TPD52 Axis. OncoTargets and therapy 42 32308433
2004 Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI. Blood 42 15576473
2015 Tumor-suppressive microRNA-34a inhibits breast cancer cell migration and invasion via targeting oncogenic TPD52. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 26678891
2021 Acetylation-dependent regulation of TPD52 isoform 1 modulates chaperone-mediated autophagy in prostate cancer. Autophagy 39 34034634
2018 Over-expression of miR-15a-3p enhances the radiosensitivity of cervical cancer by targeting tumor protein D52. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 30021370
2006 A testis-specific and testis developmentally regulated tumor protein D52 (TPD52)-like protein TPD52L3/hD55 interacts with TPD52 family proteins. Biochemical and biophysical research communications 38 16631610
2016 Tumor Protein D52 (TPD52) Inhibits Growth and Metastasis in Renal Cell Carcinoma Cells Through the PI3K/Akt Signaling Pathway. Oncology research 36 27983909
2015 TPD52 expression increases neutral lipid storage within cultured cells. Journal of cell science 34 26183179
2013 TPD52 represents a survival factor in ERBB2-amplified breast cancer cells. Molecular carcinogenesis 33 23661506
2013 Patterns of TPD52 overexpression in multiple human solid tumor types analyzed by quantitative PCR. International journal of oncology 33 24317684
2013 Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells. American journal of physiology. Gastrointestinal and liver physiology 28 23868405
2001 The role of the coiled-coil motif in interactions mediated by TPD52. Biochemical and biophysical research communications 28 11594751
2016 Downregulation of MicroRNA-449 Promotes Migration and Invasion of Breast Cancer Cells by Targeting Tumor Protein D52 (TPD52). Oncology research 27 27983918
2006 Expression of tumor protein D52-like genes in childhood leukemia at diagnosis: clinical and sample considerations. Leukemia research 27 16620967
2020 miR-103a-3p Suppresses Cell Proliferation and Invasion by Targeting Tumor Protein D52 in Prostate Cancer. Journal of investigative surgery : the official journal of the Academy of Surgical Research 26 32166986
2020 LINC01133 contribute to epithelial ovarian cancer metastasis by regulating miR-495-3p/TPD52 axis. Biochemical and biophysical research communications 24 33036757
2009 Tumor protein D52 expression and Ca2+-dependent phosphorylation modulates lysosomal membrane protein trafficking to the plasma membrane. American journal of physiology. Cell physiology 24 20032513
2020 Long Non-Coding RNA HULC Promotes Cervical Cancer Cell Proliferation, Migration and Invasion via miR-218/TPD52 Axis. OncoTargets and therapy 23 32103980
2018 Long non‑coding RNA ferritin heavy polypeptide 1 pseudogene 3 controls glioma cell proliferation and apoptosis via regulation of the microRNA‑224‑5p/tumor protein D52 axis. Molecular medicine reports 21 30221720
2020 MicroRNA‑103a‑3p promotes metastasis by targeting TPD52 in salivary adenoid cystic carcinoma. International journal of oncology 20 32467999
2013 Tumor protein D52 represents a negative regulator of ATM protein levels. Cell cycle (Georgetown, Tex.) 20 23974097
2008 Tumor protein D52 overexpression and gene amplification in cancers from a mosaic of microarrays. Critical reviews in oncogenesis 20 19105569
2020 Hsa_circ_0084927 Regulates Cervical Cancer Advancement via Regulation of the miR-634/TPD52 Axis. Cancer management and research 19 33061631
2010 A role for tumor protein TPD52 phosphorylation in endo-membrane trafficking during cytokinesis. Biochemical and biophysical research communications 19 20946871
2019 Tumor protein D52 (isoform 3) interacts with and promotes peroxidase activity of Peroxiredoxin 1 in prostate cancer cells implicated in cell growth and migration. Biochimica et biophysica acta. Molecular cell research 18 30981892
2019 Identification of TPD52 and DNAJB1 as two novel bile biomarkers for cholangiocarcinoma by iTRAQ‑based quantitative proteomics analysis. Oncology reports 18 31661142
2017 Tumor protein D52 (isoform 3) contributes to prostate cancer cell growth via targeting nuclear factor-κB transactivation in LNCaP cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 28466782
2009 Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52 administered with soluble GM-CSF. Cancer immunology, immunotherapy : CII 18 19169682
2009 Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: prolonged survival. Vaccine 18 19201387
2007 Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity. Cancer immunology, immunotherapy : CII 18 17962942
2021 Anti-osteosarcoma effect of antiserum against cross antigen TPD52 between osteosarcoma and Trichinella spiralis. Parasites & vectors 17 34565443
2019 MicroRNA-449b-5p suppresses cell proliferation, migration and invasion by targeting TPD52 in nasopharyngeal carcinoma. Journal of biochemistry 17 31350893
2019 Silencing of TPD52 inhibits proliferation, migration, invasion but induces apoptosis of pancreatic cancer cells by deactivating Akt pathway. Neoplasma 17 31847526
2016 miR-139-5p regulates proliferation, apoptosis, and cell cycle of uterine leiomyoma cells by targeting TPD52. OncoTargets and therapy 17 27785063
2023 Androgen receptor suppresses lung cancer invasion and increases cisplatin response via decreasing TPD52 expression. International journal of biological sciences 16 37564195
2014 Lentivirus-mediated knockdown of tumor protein D52-like 2 inhibits glioma cell proliferation. Cellular and molecular biology (Noisy-le-Grand, France) 16 24842331
2021 Tumor protein D52 is upregulated in oral squamous carcinoma cells under hypoxia in a hypoxia-inducible-factor-independent manner and is involved in cell death resistance. Cell & bioscience 15 34217360
2021 Tumor protein D52 promotes breast cancer proliferation and migration via the long non-coding RNA NEAT1/microRNA-218-5p axis. Annals of translational medicine 15 34277808
2017 microRNA-503 suppresses the migration, proliferation and colony formation of prostate cancer cells by targeting tumor protein D52 like 2. Experimental and therapeutic medicine 14 29375699
2016 Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 26846108
2022 MiR-125b-5p/TPD52 Axis Affects Proliferation, Migration and Invasion of Breast Cancer Cells. Molecular biotechnology 13 35320453
2022 Tumor protein D52 (TPD52) affects cancer cell metabolism by negatively regulating AMPK. Cancer medicine 13 35666017
2021 Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study. Clinical cancer research : an official journal of the American Association for Cancer Research 13 34702771
2020 Long-Noncoding RNA FGD5-AS1 Enhances the Viability, Migration, and Invasion of Glioblastoma Cells by Regulating the miR-103a-3p/TPD52 Axis. Cancer management and research 13 32848452
2008 Calcium/calmodulin-dependent phosphorylation of tumor protein D52 on serine residue 136 may be mediated by CAMK2delta6. American journal of physiology. Gastrointestinal and liver physiology 13 18832449
2020 MicroRNA-1323 downregulation promotes migration and invasion of breast cancer cells by targeting tumour protein D52. Journal of biochemistry 12 32211853
2018 MicroRNA-379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52. Experimental and therapeutic medicine 12 30116374
2017 All-Trans-Retinoic Acid Stimulates Overexpression of Tumor Protein D52 (TPD52, Isoform 3) and Neuronal Differentiation of IMR-32 Cells. Journal of cellular biochemistry 12 28436114
2014 Identification of PLP2 and RAB5C as novel TPD52 binding partners through yeast two-hybrid screening. Molecular biology reports 12 24604726
2023 AMPK targets a proto-oncogene TPD52 (isoform 3) expression and its interaction with LKB1 suppress AMPK-GSK3β signaling axis in prostate cancer. Journal of cell communication and signaling 9 37040029
2022 MiR-139-5p Inhibits the Development of Gastric Cancer through Targeting TPD52. Journal of healthcare engineering 9 35222884
2021 AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells. Cancers 9 34831003
2021 Hsa_circ_0007637 Facilitates Nasopharyngeal Carcinoma Progression by Sponging miR-636/TPD52 Axis. Cancer management and research 9 35002322
2019 Delayed recruiting of TPD52 to lipid droplets - evidence for a "second wave" of lipid droplet-associated proteins that respond to altered lipid storage induced by Brefeldin A treatment. Scientific reports 9 31278300
2015 Tumor protein D52-like 2 contributes to proliferation of breast cancer cells. Cancer biotherapy & radiopharmaceuticals 9 25629696
2008 TPD52, a candidate gene from genomic studies, is overexpressed in testicular germ cell tumours. Molecular and cellular endocrinology 9 19041365
2024 The Tumor Suppressor TPD52-Governed Endoplasmic Reticulum Stress is Modulated by APCCdc20. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39401430
2016 Dropping in on the lipid droplet- tumor protein D52 (TPD52) as a new regulator and resident protein. Adipocyte 8 27617178
2019 Star-PAP regulates tumor protein D52 through modulating miR-449a/34a in breast cancer. Biology open 7 31649118
2024 KLF7 enhances the invasion and migration of colorectal cancer cells via the miR-139-5p/TPD52 axis. Cancer biology & therapy 6 39097779
2023 Cross talk of tumor protein D52 (TPD52) with KLF9, PKCε, and MicroRNA 223 in ovarian cancer. Journal of ovarian research 6 37833790
2017 Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes. BioMed research international 6 28798933
2015 Tumor protein D52-like 2 accelerates gastric cancer cell proliferation in vitro. Cancer biotherapy & radiopharmaceuticals 6 25746840
2021 Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers. Scientific reports 5 34099820
2019 Analysis of the CD8+ IL-10+ T cell response elicited by vaccination with the oncogenic tumor-self protein D52. Human vaccines & immunotherapeutics 5 31769704
2017 Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability. The Biochemical journal 5 28298474
2014 Knockdown of tumor protein D52-like 2 induces cell growth inhibition and apoptosis in oral squamous cell carcinoma. Cell biology international 5 25262828
2023 Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR. Histology and histopathology 4 37140169
2022 Circ_0060551 promotes the migration and invasion of cervical cancer by upregulating TPD52. American journal of reproductive immunology (New York, N.Y. : 1989) 4 35716110
2022 Long Noncoding RNA DSCAM-AS1 Facilitates Proliferation and Migration of Hemangioma Endothelial Cells by Targeting miR-411-5p/TPD52 Axis. BioMed research international 4 36267843
2016 Retracted: Knockdown of tumor protein D52-like 2 induces cell growth inhibition and apoptosis in oral squamous cell carcinoma. Cell biology international 4 26909548
2024 Circular RNA circEZH2 Promotes Lung Adenocarcinoma Progression by Regulating microRNA-495-3p/Tumor Protein D52 Axis and Activating Nuclear Factor-Kappa B Pathway. International journal of general medicine 3 39359616
2025 TPD52 as a Therapeutic Target Identified by Machine Learning Shapes the Immune Microenvironment in Breast Cancer. Journal of cellular and molecular medicine 2 39757112
2025 TPD52 (isoform 3) promotes resistance to mTOR-targeted inhibitors by regulating c-Myc, PTEN, and direct activation of 4E-BP1 in LNCaP androgen-dependent cells. Biochemical and biophysical research communications 2 39983549
2025 Role of TPD52 in Endometrial Cancer: Impact on EMT and the PI3K/AKT and ERK/MAPK Signaling. Protein and peptide letters 2 41140081
2024 [Non-small cell lung cancer-derived exosomal circular RNA circEZH2 activates fibroblasts by regulating the miR-495-3p / TPD52 axis and NF-κB pathway]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 2 39690542
2023 Tumor protein D52 (isoform 3) induces NF-κB - STAT3 mediated EMT driving neuroendocrine differentiation of prostate cancer cells. The international journal of biochemistry & cell biology 2 37935328
2025 Comprehensive analysis of the LINC01122/TPD52 axis as a predictive biomarker in prostate adenocarcinoma. Scientific reports 1 40341647
2025 Dual oncogenic roles of TPD52 and TPD52L2 in gastric cancer progression via PI3K/AKT activation and immunosuppressive microenvironment remodeling. Briefings in functional genomics 1 40973691
2024 Heightened TPD52 linked to metabolic dysfunction and associated abnormalities in zebrafish. Archives of biochemistry and biophysics 1 39349129
2023 Preclinical support for tumor protein D52 as a cancer vaccine antigen. Human vaccines & immunotherapeutics 1 37904517

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