Affinage

PINX1

PIN2/TERF1-interacting telomerase inhibitor 1 · UniProt Q96BK5

Length
328 aa
Mass
37.0 kDa
Annotated
2026-06-10
90 papers in source corpus 34 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PINX1 is a multifunctional nucleolar and telomeric protein that integrates telomerase regulation, chromosome segregation, and ribosome biogenesis (PMID:11701125, PMID:19553660, PMID:24823796). It was first defined as a Pin2/TRF1-binding protein that directly binds the telomerase catalytic subunit hTERT through its C-terminal telomerase inhibitory domain (TID, residues 290–328) and potently inhibits telomerase activity, shortening telomeres when overexpressed and elongating them when depleted (PMID:11701125, PMID:20620128); binding extends to the assembled hTERT·hTR complex via the hTR-binding domain of hTERT (PMID:15381700). PINX1 is recruited to telomeres by TRF1 through a minimal sequence requiring Leu-291, an interaction needed for telomere localization and for inhibition of telomere elongation in cis (PMID:21119197), and it reciprocally stabilizes TRF1 against ubiquitin-mediated degradation, with loss of PINX1 triggering telomere DNA damage responses and chromosome instability (PMID:24415760). Beyond inhibition, PINX1 has a positive role in telomerase recruitment, promoting telomerase association with the POT1 complex and with hTERT during S phase, acting in part as a linker that brings nucleophosmin (NPM) into a ternary complex with hTERT (PMID:19117989, PMID:22749911, PMID:28255170, PMID:31210926). In mitosis, PINX1 is a microtubule-binding protein that relocalizes to the outer kinetochore (Hec1/CENP-E-dependent) and chromosome periphery (Nucleolin-dependent), where it is essential for chromosome congression and faithful segregation (PMID:19553660, PMID:19393617); its mitotic stability is controlled by Plk1-mediated phosphorylation that drives proteasomal degradation (PMID:20573420). In the nucleolus, PINX1 activates the DEAH-box RNA helicase Prp43/DHX15 through its G-patch domain to stimulate ATPase activity and drive ribosomal subunit maturation (PMID:24823796, PMID:32882145), and it promotes RNA polymerase I preinitiation complex assembly via POLR1G/UBTF, a function shut down by nutrient-starvation-induced lysine acetylation (PMID:40639785). PINX1 also functions in DNA repair, binding the ZnF3-BRCT domain of PARP1 to facilitate XRCC1 recruitment independently of its telomerase activity (PMID:39174499). Genetic studies establish PINX1 as a haploinsufficient tumor suppressor: heterozygous mice develop telomerase-dependent chromosomal instability and spontaneous tumors, while nullizygosity is embryonic lethal (PMID:21436583). PINX1 expression is transcriptionally activated by p53 and repressed by NF-κB/p65 and STAT3 (PMID:24412852, PMID:29017500, PMID:40667563).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 2001 High

    Established PINX1 as a direct, endogenous telomerase inhibitor, answering whether a TRF1-associated factor could regulate telomerase catalytic activity.

    Evidence Co-IP, in vitro TRAP telomerase assay, overexpression/RNAi, and xenograft assay in human cells

    PMID:11701125

    Open questions at the time
    • Did not resolve which hTERT domain is bound
    • Did not address PINX1 functions outside telomerase
  2. 2002 High

    Revealed a conserved second function in rRNA/snoRNA maturation via the G-patch domain, showing PINX1 is not solely a telomere factor.

    Evidence Yeast GNO1 deletion, complementation with human PINX1, Northern blot, G-patch mutagenesis

    PMID:12107183

    Open questions at the time
    • Molecular target of the G-patch domain not identified at this stage
    • Link between nucleolar and telomeric functions unresolved
  3. 2004 High

    Defined the binding mode by which PINX1 represses telomerase, showing it engages the hTR-binding domain of hTERT and the assembled hTERT·hTR complex.

    Evidence In vitro pulldown and cellular co-IP with hTERT/hTR depletion controls

    PMID:15381700

    Open questions at the time
    • Structural basis of complex binding not determined
  4. 2004 Medium

    Identified MCRS2 as an additional PINX1-associated telomerase inhibitor, expanding the inhibitory protein network.

    Evidence Yeast two-hybrid, co-IP, co-localization, in vitro TRAP, stable overexpression telomere monitoring

    PMID:15044100

    Open questions at the time
    • Mechanism of MCRS2 contribution to telomerase inhibition not dissected
    • In vivo relevance unaddressed
  5. 2009 High

    Discovered a mitotic role: PINX1 is a microtubule-binding protein at kinetochores and chromosome periphery essential for faithful segregation, distinct from telomerase regulation.

    Evidence Deconvolution and live imaging, biochemical microtubule binding, siRNA, deletion mapping

    PMID:19553660

    Open questions at the time
    • Direct microtubule-binding interface not mapped at residue level
    • Mechanistic link to its interphase telomere role unclear
  6. 2009 Medium

    Identified Nucleolin as the recruiter of PINX1 to the chromosome periphery, defining how PINX1 supports chromosome congression in mitosis.

    Evidence Reciprocal co-IP, deconvolution microscopy, Nucleolin siRNA, live mitosis imaging

    PMID:19393617

    Open questions at the time
    • Single lab
    • How Nucleolin and kinetochore recruitment pathways coordinate not resolved
  7. 2009 Medium

    Showed PINX1 has a positive role in telomerase recruitment, reconciling inhibitory and recruitment functions.

    Evidence shRNA knockdown, telomere length analysis, co-IP of telomerase with POT1 complex

    PMID:19117989

    Open questions at the time
    • Molecular basis of the switch between inhibition and recruitment not defined
    • Two methods, single lab
  8. 2009 Medium

    Demonstrated PINX1 controls TRF1 nucleolar accumulation and telomere binding, with the C-terminus required for nucleolar localization.

    Evidence Co-localization, deletion-mutant overexpression, TRF1 telomere analysis, fibrillarin co-staining

    PMID:19265708

    Open questions at the time
    • Mechanism of forced TRF1 redistribution unclear
    • Physiological versus overexpression context not separated
  9. 2010 Medium

    Mapped the functional domains: residues 290–328 constitute the TID binding hTERT, and 254–289 binds Pin2/TRF1, separating telomere targeting from telomerase inhibition.

    Evidence Domain-mapping pulldowns, in vitro TRAP with truncation mutants, telomere length analysis

    PMID:20620128

    Open questions at the time
    • Single lab
    • Structural detail of domain–partner contacts absent
  10. 2010 High

    Defined TRF1 as the recruiter of PINX1 to telomeres, with Leu-291 essential, linking localization to inhibition of telomere elongation in cis.

    Evidence Leu-291 mutagenesis, TRF1 RNAi epistasis, telomere length and telomerase activity assays, co-IP

    PMID:21119197

    Open questions at the time
    • How telomere recruitment couples to catalytic inhibition mechanistically not fully resolved
  11. 2010 High

    Established Plk1 as a negative regulator of PINX1 stability through mitotic phosphorylation-driven proteasomal degradation.

    Evidence Co-IP, in vitro kinase assay, phosphosite mutagenesis, proteasome inhibitor, knockdown/overexpression

    PMID:20573420

    Open questions at the time
    • E3 ligase mediating degradation not identified
    • Functional consequence for segregation not directly tied to phosphosites
  12. 2011 High

    Provided in vivo proof that PINX1 is a haploinsufficient tumor suppressor required for chromosome stability and telomerase control.

    Evidence PINX1 knockout/heterozygous mouse model, MEF telomerase assay, cytogenetics, tumor histopathology, p53 epistasis

    PMID:21436583

    Open questions at the time
    • Tissue-specific contributions not dissected
    • Relative weight of telomere versus mitotic functions in tumorigenesis unclear
  13. 2012 Medium

    Showed endogenous PINX1 acts at telomeres primarily in mitosis, stabilizing TRF1 and promoting timely M-phase entry.

    Evidence Telomere ChIP, siRNA knockdown, cell cycle analysis

    PMID:22331467

    Open questions at the time
    • Single lab
    • Mechanism connecting TRF1 stabilization to mitotic entry not defined
  14. 2012 Medium

    Demonstrated PINX1 directs cell-cycle-dependent trafficking of hTERT to telomeres in S phase and chromosomes in anaphase.

    Evidence Immunofluorescence co-localization, siRNA, cell-cycle synchronization

    PMID:22749911

    Open questions at the time
    • Trafficking machinery used by PINX1 not identified
    • Localization data without biochemical mechanism
  15. 2014 High

    Resolved the PINX1–TRF1–hTERT regulatory circuit, showing PINX1 stabilizes TRF1 and that hTERT plays dual roles in this stability pathway.

    Evidence siRNA, co-IP, ubiquitination assay, TIF assay, cytogenetics, ectopic hTERT, hTERT co-knockdown epistasis

    PMID:24415760

    Open questions at the time
    • Mechanism by which hTERT both supports and antagonizes TRF1 stability not fully explained
  16. 2014 Medium

    Identified p53 as a direct transcriptional activator of PINX1 and showed HPV16 E6 suppresses PINX1 by inhibiting p53, linking PINX1 regulation to viral oncogenesis.

    Evidence ChIP, luciferase reporter, p53 overexpression/knockdown, E6 expression, TRAP

    PMID:24412852

    Open questions at the time
    • Single lab
    • Other transcriptional inputs not assessed here
  17. 2014 High

    Defined PINX1 as a direct activator of the Prp43/DHX15 helicase through its G-patch domain, mechanistically explaining its ribosome biogenesis role.

    Evidence In vitro ATPase stimulation, co-IP (yeast and human), G-patch mutagenesis, sucrose gradient ribosome analysis

    PMID:24823796

    Open questions at the time
    • Structural basis of G-patch–Prp43 engagement addressed only later
    • Human cellular ribosome phenotype not fully quantified
  18. 2015 Medium

    Showed PINX1 represses ERα as a transcriptional corepressor, extending its role to nuclear receptor signaling.

    Evidence Co-IP, ChIP on E2-regulated promoters, AF-1/AF-2 reporter assays, ERα domain mapping

    PMID:26187699

    Open questions at the time
    • Corepressor mechanism (recruited complexes) not defined
    • Single lab
  19. 2015 Medium

    Identified PINX1 suppression of MMP-9 via NF-κB as a basis for inhibiting breast cancer migration and invasion.

    Evidence siRNA/overexpression, zymography, NF-κB reporter, tail-vein metastasis model

    PMID:25888829

    Open questions at the time
    • Direct molecular target in the NF-κB axis not identified
    • Single lab
  20. 2015 Medium

    Established TERT as a stabilizer of nucleolar PINX1, defining a reciprocal protein-stability relationship specific to the C-terminal fragment.

    Evidence TERT siRNA/overexpression, cycloheximide chase with truncation mutants

    PMID:26194824

    Open questions at the time
    • Mechanism of TERT-mediated stabilization unknown
    • Single lab
  21. 2017 Medium

    Showed PINX1 links NPM to hTERT, with NPM recruitment partially attenuating PINX1's telomerase inhibition.

    Evidence Co-IP, direct binding assay, TRAP, domain mapping

    PMID:28255170

    Open questions at the time
    • Quantitative balance of inhibition versus attenuation not defined
    • Single lab
  22. 2017 Medium

    Defined NF-κB p65 as a direct transcriptional repressor binding two promoter response elements of PINX1.

    Evidence EMSA, ChIP, promoter-reporter with site-directed mutagenesis

    PMID:29017500

    Open questions at the time
    • Upstream signals controlling p65 occupancy not addressed here
  23. 2017 Medium

    Revealed PINX1 as an EV71 3C protease substrate, cleaved at Q50–G51 to promote apoptosis and viral release, identifying a host-pathogen vulnerability.

    Evidence Co-IP, in vitro cleavage assay, overexpression/siRNA, apoptosis and viral release assays

    PMID:27847364

    Open questions at the time
    • Consequences of cleavage for PINX1's other functions not mapped
    • Single lab
  24. 2019 Medium

    Showed PINX1 represses tumor angiogenesis by transcriptionally activating miR-125a-3p to suppress VEGF.

    Evidence miRNA microarray, ChIP, luciferase reporter, siRNA, angiogenesis assay, xenograft

    PMID:31254127

    Open questions at the time
    • How a telomerase regulator acts as a direct transcriptional activator mechanistically unclear
    • Single lab
  25. 2019 Medium

    Refined the cell-cycle timing of the NPM/PINX1/hTERT ternary complex to early S phase, tying it to telomere extension.

    Evidence Immunofluorescence, synchronization, co-IP, TRF telomere assay

    PMID:31210926

    Open questions at the time
    • Single lab
    • Causal contribution of complex timing to net telomerase output not isolated
  26. 2019 Medium

    Showed EBV LMP1 represses PINX1 by enhancing NF-κB p65 promoter binding, increasing telomerase activity, connecting viral oncogenesis to PINX1 control.

    Evidence ChIP, dual-luciferase reporter, LMP1 overexpression, TRAP, Southern blot

    PMID:31027734

    Open questions at the time
    • Single lab
    • Direct versus indirect effect of LMP1 on p65 not fully separated
  27. 2020 High

    Defined distinct structural binding modes of PINX1 versus Pfa1 G-patches to Prp43 while showing both require the OB-fold β4–β5 loop for ATPase/helicase stimulation.

    Evidence In vitro ATPase and helicase assays, Prp43 loop mutants in yeast, co-IP, ribosome biogenesis analysis

    PMID:32882145

    Open questions at the time
    • Full structural model of human PINX1–DHX15 complex not solved
    • Functional impact in human cells not directly tested
  28. 2024 High

    Identified a telomerase-independent DNA repair function: PINX1 binds the PARP1 ZnF3-BRCT domain to promote PARP1-chromatin loading and XRCC1 recruitment.

    Evidence IP-MS, co-IP with domain specificity, chromatin fractionation, γH2AX assays, rescue with telomerase-inhibitory mutant

    PMID:39174499

    Open questions at the time
    • Which DNA repair pathways depend on PINX1 not fully mapped
    • Structural detail of PARP1 interaction absent
  29. 2024 Low

    Reported PINX1 interaction with RBM10 as a possible contributor to telomere maintenance modulating radiation immunostimulation.

    Evidence IP-MS interactor identification, radiosensitivity assays, cGAS-STING western blot

    PMID:38431575

    Open questions at the time
    • IP-MS identification with limited mechanistic follow-up for the specific PINX1-RBM10 mechanism
    • Causality of telomere effect not established
    • Single lab
  30. 2025 High

    Defined PINX1's role in RNA Pol I preinitiation complex assembly via POLR1G/UBTF and showed nutrient-starvation acetylation disrupts this to shut down rDNA transcription.

    Evidence Co-IP (PINX1-POLR1G-UBTF), MS acetylation site mapping, acetyl-site mutagenesis, rDNA transcription and ribosome biogenesis assays

    PMID:40639785

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes not identified
    • Integration with the DHX15 ribosome function not resolved
  31. 2025 Medium

    Showed PINX1 promotes SPOP-mediated ILF3 ubiquitination to suppress PI3K-AKT-mTOR signaling and enhance cisplatin sensitivity, with STAT3 repressing PINX1 transcription.

    Evidence Co-IP, ubiquitination assay, ChIP, dual-luciferase, cell cycle and IC50 assays

    PMID:40667563

    Open questions at the time
    • Whether PINX1 acts directly in the ubiquitination complex unclear
    • Single lab
  32. 2026 Medium

    Reported a TID-dependent PINX1–Rab11a–RanBP2 axis driving Rab11a SUMOylation and degradation to impair migrasome formation and reduce cisplatin resistance.

    Evidence Co-IP, immunofluorescence, ChIP (TP53 on promoter), Rab11a SUMOylation assay, domain mapping, migrasome and resistance assays

    PMID:42086676

    Open questions at the time
    • Whether PINX1 directly catalyzes or scaffolds SUMOylation unclear
    • Single lab
    • Generalizability beyond nasopharyngeal carcinoma untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PINX1's many functions—telomerase regulation, kinetochore/microtubule binding, RNA Pol I and DHX15-driven ribosome biogenesis, DNA repair, and nuclear receptor coregulation—are coordinated within one protein and partitioned across cell-cycle phases and subcellular compartments remains unresolved.
  • No unifying structural model integrating the TID, G-patch, and TRF1-binding domains
  • No comprehensive map of which functions dominate in physiological versus disease contexts
  • Regulatory hierarchy among p53, NF-κB, and STAT3 transcriptional inputs not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005730 nucleolus 4 GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-73894 DNA Repair 1
Partners
DHX15NPMPARP1POLR1GPOT1TERTTRF1UBTF
Complex memberships
RNA polymerase I preinitiation complexkinetochoretelomerase (hTERT·hTR) complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PinX1 was identified as a Pin2/TRF1-binding protein that directly binds the telomerase catalytic subunit hTERT via its TID (telomerase inhibitory domain) and potently inhibits telomerase activity in vitro and in vivo. Overexpression inhibits telomerase, shortens telomeres, and induces crisis; depletion increases telomerase activity and elongates telomeres. Co-immunoprecipitation, in vitro telomerase inhibition assay (TRAP), overexpression and RNAi depletion in human cells, xenograft tumorigenicity assay Cell High 11701125
2002 The yeast homolog of PinX1 (Gno1p) is involved in rRNA and snoRNA maturation; its G-patch domain is essential for both rRNA processing and snoRNA maturation. PinX1 complements the gno1Δ mutation, indicating a conserved dual function in telomere regulation and rRNA maturation consistent with its nucleolar localization. Yeast genetics (GNO1 deletion), complementation assay with human PinX1, Northern blot, mutational analysis of G-patch domain The Journal of biological chemistry High 12107183
2004 PinX1 binds directly to hTERT protein (primarily to its hTR-binding domain) in vitro, and also associates with hTR in a cellular context dependent on hTERT presence, suggesting PinX1 represses telomerase by binding the assembled hTERT·hTR complex. In vitro binding assays (pulldown), co-immunoprecipitation in cells with hTERT/hTR depletion controls The Journal of biological chemistry High 15381700
2009 PinX1 is a novel microtubule-binding protein that localizes to nucleoli and telomeres in interphase and relocalizes to chromosome periphery and the outer kinetochore plate in mitosis. Kinetochore localization depends on Hec1 and CENP-E. Depletion by siRNA causes anaphase chromatid bridges and micronuclei, demonstrating an essential role in faithful chromosome segregation. Deconvolution microscopy, deletion mapping, siRNA knockdown, real-time imaging, biochemical microtubule-binding assay The Journal of biological chemistry High 19553660
2009 Silencing PinX1 in telomerase-positive cancer cells causes robust telomere shortening and reduces the endogenous association of telomerase with the POT1-containing telomeric protein complex, revealing a positive role for PinX1 in telomerase recruitment to telomeres. shRNA knockdown, telomere length analysis, co-immunoprecipitation of telomerase with POT1 complex Cancer research Medium 19117989
2009 PinX1 interacts with Nucleolin at chromosome periphery via its C-terminus; Nucleolin depletion abolishes PinX1 chromosome-periphery localization, and co-depletion of both proteins abrogates chromosome congression, indicating PinX1 is recruited to chromosome periphery by Nucleolin to facilitate chromosome congression. Co-immunoprecipitation, deconvolution microscopy, siRNA depletion of Nucleolin, real-time mitosis imaging Biochemical and biophysical research communications Medium 19393617
2009 PinX1 regulates nucleolar accumulation and telomeric association of TRF1: overexpressed PinX1 forces endogenous TRF1 into the nucleolus and upregulates TRF1 binding to telomeres; the C-terminal region of PinX1 is required for nucleolar localization. Co-localization studies, overexpression of deletion mutants, TRF1 telomere ChIP-like analysis, fibrillarin co-staining Journal of molecular biology Medium 19265708
2010 PinX1 is recruited to telomeres by TRF1 via the TRF homology domain of TRF1 interacting with a minimal 20-amino-acid sequence of PinX1; disrupting this interaction by mutating Leu-291 of PinX1 or knocking down TRF1 abolishes telomere localization of PinX1 and its ability to inhibit telomere elongation, without affecting telomerase activity per se. Mutagenesis (Leu-291 substitution), RNAi of TRF1, telomere length assay, telomerase activity assay, co-immunoprecipitation, domain-mapping The Journal of biological chemistry High 21119197
2010 Polo-like kinase 1 (Plk1) interacts with PinX1 and phosphorylates it at five sites in mitosis; Plk1 overexpression promotes PinX1 proteasomal degradation dependent on ubiquitin, while Plk1 depletion increases PinX1 stability, establishing Plk1 as a negative regulator of PinX1 stability via mitotic phosphorylation. Co-immunoprecipitation, in vitro kinase assay, overexpression/siRNA depletion, proteasome inhibitor treatment, phosphosite mutagenesis European journal of cell biology High 20573420
2010 Anthracyclines downregulate PinX1 protein through the ubiquitin-proteasome pathway, thereby disrupting PinX1-mediated telomerase recruitment to telomeres and causing telomere dysfunction specifically in telomerase-positive cancer cells. Western blot, ubiquitination assay, proteasome inhibitor rescue, telomerase association assay (co-IP), telomere dysfunction assays in cancer cells Oncogene Medium 21643006
2010 The C-terminal fragment of LPTS/PinX1 (residues 290–328) is the telomerase inhibitory domain (TID) that directly associates with hTERT and shows stronger in vitro telomerase inhibitory activity than full-length protein; residues 254–289 mediate binding to Pin2/TRF1; overexpression of 290–328 shortens telomeres while expression of dominant-negative 1–289 elongates them. Domain-mapping pulldowns, in vitro TRAP telomerase assay with truncation mutants, overexpression of fragments in cells with telomere length analysis Biochemical and biophysical research communications Medium 20620128
2011 PinX1 heterozygosity in mice activates telomerase and leads to telomerase-dependent chromosomal instability; PinX1-null mice are embryonic lethal; most PinX1+/- mice spontaneously develop malignant tumors with chromosome instability, establishing PinX1 as a haploinsufficient tumor suppressor essential for chromosome stability. PinX1 knockout/heterozygous mouse model, MEF telomerase activity assay, cytogenetic chromosome instability analysis, tumor histopathology, p53 mutant epistasis cross The Journal of clinical investigation High 21436583
2012 Endogenous PinX1 associates with telomeres primarily at mitosis; knockdown of PinX1 causes delayed mitotic entry and reduces accumulation of TRF1 on telomeres during mitosis, indicating PinX1 stabilizes TRF1 at mitosis to promote M phase entry. Chromatin immunoprecipitation (telomere ChIP), siRNA knockdown, cell cycle analysis Molecular and cellular biology Medium 22331467
2012 PinX1 is involved in cell-cycle-dependent trafficking of hTERT to telomeres during mid-late S phase; PinX1 silencing reduces telomerase localization to telomeres and also mediates chromosomal localization of hTERT during anaphase. Immunofluorescence co-localization, siRNA silencing, cell-cycle synchronization FEBS letters Medium 22749911
2014 PinX1 overexpression stabilizes TRF1 protein; PinX1 depletion leads to TRF1 ubiquitination and degradation and reduced TRF1 telomere association, causing DNA damage responses at telomeres and chromosome instability. hTERT plays dual roles in this pathway: it is required for PinX1-mediated TRF1 stability, yet co-knockdown of PinX1 and hTERT restores TRF1 stability and suppresses chromosome instability. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, telomere dysfunction-induced foci (TIF) assay, cytogenetics, ectopic hTERT expression The Journal of biological chemistry High 24415760
2014 Yeast Gno1p and human PINX1 activate the DEAH-box RNA helicase Prp43p (human DHX15) via their G-patch domain, stimulating its ATPase activity in vitro; this interaction is required for maturation of pre-40S and pre-60S ribosomal particles in yeast. PINX1 interacts with human PRP43/DHX15 in HeLa cells. In vitro ATPase stimulation assay, co-immunoprecipitation (yeast and human cells), G-patch mutagenesis, ribosome biogenesis analysis (sucrose gradient sedimentation) Nucleic acids research High 24823796
2015 PinX1 inhibits breast cancer cell migration and invasion by suppressing MMP-9 expression and activity via NF-κB-dependent transcription. siRNA/overexpression in breast cancer cells, gelatin zymography, western blot, NF-κB reporter assay, nude mouse tail-vein metastasis model Molecular cancer Medium 25888829
2015 PINX1 interacts with the N-terminal domain of estrogen receptor alpha (ERα) and functions as a transcriptional corepressor, repressing both AF-1 and AF-2 transcriptional activities; ChIP assays confirmed the ERα-PINX1 interaction on E2-regulated promoters. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assay (AF-1/AF-2 activity), ERα domain mapping, proliferation assays Molecular and cellular endocrinology Medium 26187699
2017 Nucleophosmin (NPM) directly interacts with PinX1; PinX1 acts as a linker between NPM and hTERT, and NPM recruitment to the telomerase complex by PinX1 partially attenuates PinX1-mediated telomerase inhibition. Co-immunoprecipitation, direct binding assay, telomerase activity assay (TRAP), domain mapping Scientific reports Medium 28255170
2017 EV71 viral protease 3C directly interacts with PinX1 and cleaves it at the Q50–G51 site via its protease activity; this cleavage promotes host cell apoptosis and facilitates EV71 release. Co-immunoprecipitation of 3C and PinX1, in vitro cleavage assay with 3C protease, overexpression/siRNA, apoptosis assay, viral release measurement Journal of virology Medium 27847364
2017 NF-κB p65 directly binds two consensus response elements in the LPTS/PinX1 promoter (at −1143/−1136 and −888/−881) and transcriptionally represses LPTS/PinX1 expression; mutation of both sites rescues p65-suppressed promoter activity. EMSA (electrophoretic mobility shift assay), chromatin immunoprecipitation (ChIP), promoter-reporter assay with site-directed mutagenesis Cell communication and signaling Medium 29017500
2019 PinX1 transcriptionally activates miR-125a-3p expression, which in turn inhibits VEGF (a miR-125a-3p target), thereby repressing tumor angiogenesis in renal cell carcinoma; ChIP and luciferase reporter assays confirmed the transcriptional mechanism. miRNA microarray, chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA, in vitro angiogenesis assay, xenograft model Angiogenesis Medium 31254127
2019 The PinX1/NPM interaction peaks during early S phase; NPM localization in the nucleolus during S phase requires PinX1, and the NPM/PinX1/hTERT ternary complex forms predominantly in early S phase, facilitating telomerase activation when telomere extension occurs. Immunofluorescence co-localization, cell cycle synchronization, co-immunoprecipitation, telomere length assay (TRF assay) Cell & bioscience Medium 31210926
2019 EBV LMP1 inhibits PINX1 transcription by promoting binding of NF-κB p65 to three specific sites in the PINX1 promoter, resulting in increased telomerase activity and telomere elongation. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, LMP1 overexpression, TRAP telomerase assay, Southern blot for telomere length Biochemical and biophysical research communications Medium 31027734
2020 The G-patch binding modes of Pfa1 and PINX1 to Prp43 are distinct: a protruding β4–β5 loop of Prp43 OB fold is required for Pfa1 G-patch binding but not for PINX1 binding. However, this same loop is essential for stimulation of Prp43 ATPase and helicase activities by both proteins and for Prp43 function in ribosome biogenesis. In vitro ATPase assay, helicase assay, yeast genetics (Prp43 loop mutants), co-immunoprecipitation, ribosome biogenesis analysis RNA biology High 32882145
2014 PinX1 regulates TRF1 stability in a PinX1-telomere binding manner: the LPTS/PinX1(254–289) fragment binds Pin2/TRF1 while LPTS/PinX1(290–328) binds hTERT; Pin2/TRF1 interaction recruits PinX1 to telomeres. Domain deletion analysis, co-immunoprecipitation, in vitro telomerase inhibition assay, cellular telomere length analysis Biochemical and biophysical research communications Medium 20620128
2014 p53 functions as a transcriptional activator of PinX1 expression by directly binding the PinX1 promoter; HPV16 E6 suppresses PinX1 expression by inhibiting p53 transcriptional activity, thereby enhancing telomerase activity. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, p53 overexpression/knockdown, E6 expression, TRAP telomerase assay Biochimica et biophysica acta Medium 24412852
2015 TERT stabilizes nucleolar PinX1 protein: PinX1 stability is reduced in TERT-depleted cells and increased in TERT-overexpressing cells; this effect is specific to the C-terminal nucleolar fragment PinX1(205–328) that binds TERT, not the N-terminal nuclear fragment. TERT siRNA knockdown and overexpression, protein stability assays (cycloheximide chase) with truncation mutants Molecules and cells Medium 26194824
2024 PINX1 is an uncharacterized PARP1-interacting protein: it binds to the ZnF3-BRCT domain of PARP1, promotes PARP1-chromatin association, and facilitates downstream recruitment of the DNA repair factor XRCC1. Loss of PINX1 compromises DNA damage repair capacity, and this vulnerability is independent of its telomerase inhibitory activity. Immunoprecipitation-mass spectrometry (for interactor identification), co-immunoprecipitation, chromatin fractionation, DNA damage assays (γH2AX), rescue with telomerase-inhibitory mutant PINX1, XRCC1 recruitment assay Cell death & disease High 39174499
2025 PinX1 regulates ribosome biogenesis by binding RNA polymerase I subunit POLR1G (required for RNA pol I preinitiation complex assembly) in association with UBTF. Upon nutrient starvation, PinX1 is acetylated at multiple lysine residues (K43, K133, K140, K149, K190, K222), which disrupts its binding to POLR1G and leads to disassembly of the RNA pol I preinitiation complex, shutting down rDNA transcription. Co-immunoprecipitation (PinX1-POLR1G-UBTF), mass spectrometry identification of acetylation sites, mutagenesis of acetylation sites, rDNA transcription assay, ribosome biogenesis assay, nutrient starvation experiments The Journal of biological chemistry High 40639785
2026 PinX1 (activated transcriptionally by TP53) binds Rab11a via its telomerase inhibitory domain (aa 252–328), recruits RanBP2 to Rab11a, and induces SUMOylation of Rab11a at K207, leading to Rab11a degradation; this impairs migrasome formation and mitochondrial transfer, reducing cisplatin resistance in nasopharyngeal carcinoma cells. Co-immunoprecipitation, immunofluorescence, ChIP (TP53 on PinX1 promoter), Rab11a SUMOylation assay, domain-mapping (TID 252–328), migrasome formation assay, cisplatin resistance assay Oncogene Medium 42086676
2025 PINX1 promotes ILF3 ubiquitination via the E3 ligase SPOP, leading to ILF3 degradation and suppression of the PI3K-AKT-mTOR pathway; this inhibits tumor proliferation and enhances cisplatin sensitivity in nasopharyngeal carcinoma. STAT3 suppresses PINX1 transcription (confirmed by ChIP and dual-luciferase assay). Co-immunoprecipitation, ubiquitination assay, chromatin immunoprecipitation, dual-luciferase assay, western blot, cell cycle and IC50 assays American journal of cancer research Medium 40667563
2004 MCRS2 (an isoform of MCRS1/p78) interacts with LPTS/PinX1 in vitro and in vivo, co-localizes with it in cells, and inhibits telomerase activity in vitro; long-term MCRS2 overexpression causes progressive telomere shortening. Yeast two-hybrid (initial identification), co-immunoprecipitation, co-localization microscopy, in vitro telomerase inhibition assay (TRAP), stable overexpression with telomere length monitoring Biochemical and biophysical research communications Medium 15044100
2010 PinX1 inhibits telomerase activity in gastric cancer cells through upregulation of Mad1 and downregulation of c-Myc; PinX1 RNAi produces the opposite effect (downregulation of Mad1, upregulation of c-Myc), placing PinX1 upstream of the Mad1/c-Myc pathway in telomerase regulation. Transfection of PinX1 and PinX1-siRNA, TRAP telomerase assay, RT-PCR and western blot for Mad1/c-Myc Journal of gastrointestinal surgery Low 20544396
2024 PinX1 interacts with RBM10 (identified by immunoprecipitation-mass spectrometry); this interaction may assist telomerase localization to telomeres and promote telomere maintenance, thereby inhibiting immunostimulatory effects of ionizing radiation. Immunoprecipitation-mass spectrometry (for interactor identification), functional radiosensitivity assays, cGAS-STING pathway western blot Journal of translational medicine Low 38431575

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 266 11701125
2002 The yeast homolog of human PinX1 is involved in rRNA and small nucleolar RNA maturation, not in telomere elongation inhibition. The Journal of biological chemistry 76 12107183
2004 Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR. The Journal of biological chemistry 65 15381700
2011 The telomerase inhibitor PinX1 is a major haploinsufficient tumor suppressor essential for chromosome stability in mice. The Journal of clinical investigation 53 21436583
2015 PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway. Molecular cancer 49 25888829
2009 Silencing PinX1 compromises telomere length maintenance as well as tumorigenicity in telomerase-positive human cancer cells. Cancer research 46 19117989
2014 The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis. Nucleic acids research 43 24823796
2009 PinX1 is a novel microtubule-binding protein essential for accurate chromosome segregation. The Journal of biological chemistry 43 19553660
2019 PinX1 represses renal cancer angiogenesis via the mir-125a-3p/VEGF signaling pathway. Angiogenesis 39 31254127
2011 Anthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation. Oncogene 37 21643006
2010 Telomerase inhibitor PinX1 provides a link between TRF1 and telomerase to prevent telomere elongation. The Journal of biological chemistry 36 21119197
2017 Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein. Journal of virology 35 27847364
2005 Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma. Oncogene 35 15637589
2004 Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length. Biochemical and biophysical research communications 33 15044100
2010 Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions. The Journal of antibiotics 32 21102596
2013 The telomere/telomerase binding factor PinX1 is a new target to improve the radiotherapy effect of oesophageal squamous cell carcinomas. The Journal of pathology 31 23341363
2013 PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway. Molecular cancer 31 24268029
2012 PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells. Journal of experimental & clinical cancer research : CR 30 22316341
2002 Genetic analysis of the liver putative tumor suppressor (LPTS) gene in hepatocellular carcinomas. Cancer letters 29 11867205
2014 The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human cervical squamous cell carcinomas. Cancer letters 27 25045845
2004 Molecular analysis of PinX1 in medulloblastomas. International journal of cancer 27 14750185
2014 Reduced expression of PinX1 correlates to progressive features in patients with prostate cancer. Cancer cell international 25 24936151
2017 The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway. Molecular cancer 23 28372542
2022 Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1. Frontiers in pharmacology 21 35847001
2009 Human PinX1 mediates TRF1 accumulation in nucleolus and enhances TRF1 binding to telomeres. Journal of molecular biology 21 19265708
2010 PinX1 inhibits telomerase activity in gastric cancer cells through Mad1/c-Myc pathway. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 20 20544396
2010 Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1. Leukemia 20 21102426
2008 The correlation of genetic instability of PINX1 gene to clinico-pathological features of gastric cancer in the Chinese population. Journal of cancer research and clinical oncology 20 18784941
2004 Mutational analysis of PINX1 in hereditary prostate cancer. The Prostate 20 15264240
2002 Over-expression of LPTS-L in hepatocellular carcinoma cell line SMMC-7721 induces crisis. World journal of gastroenterology 20 12439923
2012 PinX1 localizes to telomeres and stabilizes TRF1 at mitosis. Molecular and cellular biology 19 22331467
2012 PinX1 is involved in telomerase recruitment and regulates telomerase function by mediating its localization. FEBS letters 19 22749911
2019 Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease. JAMA neurology 18 31058951
2016 PinX1: structure, regulation and its functions in cancer. Oncotarget 17 27556185
2014 PinX1, a telomere repeat-binding factor 1 (TRF1)-interacting protein, maintains telomere integrity by modulating TRF1 homeostasis, the process in which human telomerase reverse Transcriptase (hTERT) plays dual roles. The Journal of biological chemistry 17 24415760
2011 PinX1: a sought-after major tumor suppressor at human chromosome 8p23. Oncotarget 17 22021332
2020 Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting. Journal of experimental & clinical cancer research : CR 16 32028978
2013 Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells. Oncology reports 16 23912465
2014 PinX1-siRNA/mPEG-PEI-SPION combined with doxorubicin enhances the inhibition of glioma growth. Experimental and therapeutic medicine 15 24940406
2010 HIV-Tat-mediated delivery of an LPTS functional fragment inhibits telomerase activity and tumorigenicity of hepatoma cells. Gastroenterology 15 20816839
2009 PinX1 is recruited to the mitotic chromosome periphery by Nucleolin and facilitates chromosome congression. Biochemical and biophysical research communications 15 19393617
2022 UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury. Journal of diabetes research 14 35734237
2011 PinX1 the tail on the chromosome. The Journal of clinical investigation 14 21436580
2007 Rat homolog of PinX1 is a nucleolar protein involved in the regulation of telomere length. Gene 13 17624691
2004 Molecular analysis of PinX1 in human hepatocellular carcinoma. Oncology reports 13 15375513
2021 PINX1 promotes malignant transformation of thyroid cancer through the activation of the AKT/MAPK/β-catenin signaling pathway. American journal of cancer research 12 34873474
2017 Nucleophosmin Interacts with PIN2/TERF1-interacting Telomerase Inhibitor 1 (PinX1) and Attenuates the PinX1 Inhibition on Telomerase Activity. Scientific reports 12 28255170
2004 Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma. Oncology reports 12 15010887
2017 Low expression of PinX1 is associated with malignant behavior in basal-like breast cancer. Oncology reports 11 28586040
2015 PinX1 inhibits cell proliferation, migration and invasion in glioma cells. Medical oncology (Northwood, London, England) 11 25698538
2011 Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression. Journal of clinical pathology 11 21778296
2010 Plk1-mediated mitotic phosphorylation of PinX1 regulates its stability. European journal of cell biology 11 20573420
2010 C-terminal amino acids 290-328 of LPTS/PinX1 confer telomerase inhibition. Biochemical and biophysical research communications 11 20620128
2008 Identification of zebrafish LPTS: a gene with similarities to human LPTS/PinX1 that inhibits telomerase activity. Gene 11 18583067
2018 The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 10 30138944
2015 Suppression of PinX1 resulted in telomere dysfunction and enhanced radiosensitivity in osteosarcoma cell lines. Neoplasma 10 26458319
2015 PinX1 is up-regulated and associated with poor patients' survival in gliomas. International journal of clinical and experimental pathology 9 26261583
2014 PinX1 without the G-patch motif suppresses proliferation, induces senescence, but does not inhibit telomerase activity in colorectal cancer SW480 cells. Oncology reports 9 24839934
2020 The G-patch activators Pfa1 and PINX1 exhibit different modes of interaction with the Prp43 RNA helicase. RNA biology 8 32882145
2017 Expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous cell carcinoma. Oncology letters 8 28693215
2014 PinX1, a novel target gene of p53, is suppressed by HPV16 E6 in cervical cancer cells. Biochimica et biophysica acta 8 24412852
2011 PinX1 gene transfection enhances the sensitivity of gastric carcinoma cell line to 5-fluorouracil. Hepato-gastroenterology 8 21661452
2024 Silencing PinX1 enhances radiosensitivity and antitumor-immunity of radiotherapy in non-small cell lung cancer. Journal of translational medicine 7 38431575
2021 PinX1 Depletion Improves Liver Injury in a Mouse Model of Nonalcoholic Fatty Liver Disease via Increasing Telomerase Activity and Inhibiting Apoptosis. Cytogenetic and genome research 7 34657040
2019 The PinX1/NPM interaction associates with hTERT in early-S phase and facilitates telomerase activation. Cell & bioscience 7 31210926
2015 Novel role for PINX1 as a coregulator of nuclear hormone receptors. Molecular and cellular endocrinology 7 26187699
2019 Insufficient PINX1 expression stimulates telomerase activation by direct inhibition of EBV LMP1-NF-κB axis during nasopharyngeal carcinoma development. Biochemical and biophysical research communications 6 31027734
2017 NF-κB potentiates tumor growth by suppressing a novel target LPTS. Cell communication and signaling : CCS 6 29017500
2020 PinX1t, a Novel PinX1 Transcript Variant, Positively Regulates Cardiogenesis of Embryonic Stem Cells. Journal of the American Heart Association 5 32157956
2017 Genetic profile and biological implication of PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) in human cancers: an analysis using The Cancer Genome Atlas. Oncotarget 5 28978030
2015 Increased Stability of Nucleolar PinX1 in the Presence of TERT. Molecules and cells 5 26194824
2004 Cloning and characterization of the promoter region of human LPTS/PinX1 gene. Biochimica et biophysica acta 5 14984932
2024 PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells. Cell death & disease 4 39174499
2021 Oncogenic role of PinX1 in prostate cancer cells through androgen receptor dependent and independent mechanisms. The Journal of steroid biochemistry and molecular biology 4 33647521
2018 The clinical significance of PINX1 expression in papillary thyroid carcinoma. Human pathology 4 30026037
2017 Association between the PINX1 and NAT2 polymorphisms and serum lipid levels. Oncotarget 4 29371971
2016 Association of PINX1 but not TEP1 Polymorphisms with Progression to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B Virus Infection. Asian Pacific journal of cancer prevention : APJCP 4 27221889
2021 Regulation of PINX1 expression ameliorates lipopolysaccharide-induced lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity. Aging 3 33819185
2025 Acetylation of microtubule-binding PinX1 orchestrates ribosome biogenesis to nutrient starvation via the RNA polymerase I preinitiation complex. The Journal of biological chemistry 2 40639785
2024 PinX1 plays multifaceted roles in human cancers: a review and perspectives. Molecular biology reports 2 39550726
2023 PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma. Frontiers in bioscience (Landmark edition) 2 37664923
2021 Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations. Journal of immunology research 2 34337078
2016 Biological significance of PinX1 telomerase inhibitor in esophageal carcinoma treatment. Experimental and therapeutic medicine 2 27698711
2015 LPTS: A Novel Tumor Suppressor Gene and a Promising Drug Target for Cancer Intervention. Recent patents on anti-cancer drug discovery 2 25479038
2022 Inhibition Mechanism of PinX1 Gene on Cancer Stem Cells of Nasopharyngeal Carcinoma. Cellular and molecular biology (Noisy-le-Grand, France) 1 37114251
2026 PinX1 inhibits migrasomes-mediated mitochondrial transfer to confer cisplatin sensitivity in nasopharyngeal carcinoma. Oncogene 0 42086676
2025 PINX1 inhibits proliferation and cisplatin resistance in nasopharyngeal carcinoma by promoting ILF3 ubiquitination. American journal of cancer research 0 40667563
2025 Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1. Frontiers in oncology 0 40896430
2015 [Influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin]. Zhonghua yi xue za zhi 0 26710702
2007 [Preparation of a novel telomerase inhibitory protein LPTS-L]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 18051864

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