Affinage

PINX1

PIN2/TERF1-interacting telomerase inhibitor 1 · UniProt Q96BK5

Length
328 aa
Mass
37.0 kDa
Annotated
2026-04-28
89 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PINX1 is a multifunctional nucleolar protein that integrates telomere homeostasis, ribosome biogenesis, DNA damage repair, and chromosome segregation. Its C-terminal telomerase inhibitory domain (TID, residues 290–328) directly binds hTERT to inhibit telomerase activity, while an adjacent region (residues 254–289) binds TRF1 to recruit PINX1 to telomeres and stabilize TRF1 protein, with PINX1 haploinsufficiency causing telomerase-dependent chromosomal instability and spontaneous tumorigenesis in mice (PMID:11701125, PMID:21119197, PMID:24415760, PMID:21436583). Through its N-terminal G-patch domain, PINX1 activates the RNA helicase DHX15/Prp43 to drive pre-rRNA processing and ribosome biogenesis, and it also binds POLR1G to promote RNA Pol I preinitiation complex assembly, a function negatively regulated by acetylation during nutrient starvation (PMID:24823796, PMID:12107183, PMID:40639785). Independent of its telomerase inhibitory activity, PINX1 binds the ZnF3-BRCT domain of PARP1 to recruit XRCC1 and facilitate DNA damage repair, and during mitosis it localizes to kinetochores via Hec1/CENP-E and to chromosome periphery via Nucleolin to ensure faithful chromosome segregation, with its mitotic stability controlled by Plk1-mediated phosphorylation and proteasomal degradation (PMID:39174499, PMID:19553660, PMID:20573420).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    The foundational question of what PINX1 does was answered when it was identified as a potent endogenous telomerase inhibitor that directly binds hTERT; overexpression shortened telomeres while depletion increased telomerase activity, establishing PINX1 as a negative regulator of telomere maintenance.

    Evidence Co-immunoprecipitation, TRAP assay, gain- and loss-of-function in human cells

    PMID:11701125

    Open questions at the time
    • Mechanism of inhibition (competitive vs. allosteric) not resolved
    • In vivo physiological role in organismal context unknown
    • Whether PINX1 has telomerase-independent functions not addressed
  2. 2002 High

    The question of whether PINX1's nucleolar localization reflected a role in ribosome biogenesis was answered when the yeast ortholog Gno1p was shown to be essential for pre-rRNA processing via its G-patch domain, and human PINX1 complemented its loss, establishing an evolutionarily conserved role in rRNA maturation.

    Evidence Yeast deletion, rRNA processing assays, G-patch mutagenesis, cross-species complementation

    PMID:12107183

    Open questions at the time
    • Specific RNA substrates or snoRNAs requiring PINX1 in human cells not identified
    • Relationship between ribosome biogenesis and telomerase inhibition functions unclear
  3. 2004 High

    How PINX1 engages the telomerase holoenzyme was clarified by showing it binds directly to hTERT's hTR-binding domain and associates with the assembled hTERT·hTR complex, establishing that PINX1 targets the active ribonucleoprotein rather than free hTERT alone.

    Evidence In vitro direct binding assays, co-IP with hTERT depletion, domain mapping

    PMID:15381700

    Open questions at the time
    • Structural basis of the PINX1–hTERT interface unknown
    • Whether PINX1 displaces hTR or acts allosterically not determined
  4. 2009 High

    Whether PINX1 has mitotic functions was resolved by demonstrating it binds microtubules and localizes to kinetochores (via Hec1/CENP-E) and chromosome periphery (via Nucleolin) during mitosis; depletion caused anaphase bridges and micronuclei, establishing a telomerase-independent role in chromosome segregation.

    Evidence Deconvolution microscopy, siRNA knockdown, biochemical microtubule binding, co-IP with Nucleolin

    PMID:19393617 PMID:19553660

    Open questions at the time
    • Molecular mechanism by which PINX1 promotes segregation fidelity not defined
    • Whether microtubule binding is direct or mediated by kinetochore factors unclear
  5. 2009 High

    The relationship between PINX1, TRF1, and telomere access was clarified: PINX1 recruits TRF1 to telomeres and mediates telomerase complex association with POT1-containing shelterin, and its telomere localization depends on TRF1 interaction via a 20-amino-acid motif, establishing PINX1 as a bridge between telomerase and shelterin.

    Evidence Mutagenesis, RNAi epistasis, co-IP, telomere length assays, localization in ALT vs. telomerase-positive cells

    PMID:19117989 PMID:19265708 PMID:21119197

    Open questions at the time
    • Whether PINX1 simultaneously binds TRF1 and hTERT or forms mutually exclusive complexes unknown
    • Stoichiometry of PINX1 at telomeres not determined
  6. 2010 Medium

    The minimal telomerase inhibitory domain was mapped to residues 290–328 (TID) with stronger activity than full-length PINX1, and the adjacent region (254–289) was shown to bind TRF1 specifically, resolving the modular architecture of PINX1's C-terminus into separable telomerase-inhibition and telomere-targeting functions.

    Evidence Domain deletion mapping, GST pulldown, in vitro TRAP assay

    PMID:20620128

    Open questions at the time
    • Structural basis of TID–hTERT interaction lacking
    • Whether TRF1-binding and hTERT-binding regions cooperate in cis not tested
  7. 2010 High

    How PINX1 protein levels are regulated during mitosis was established by showing Plk1 phosphorylates PINX1 at five sites to promote its ubiquitin-proteasome-dependent degradation, explaining cell-cycle-dependent fluctuations in PINX1 abundance.

    Evidence In vitro kinase assay, phosphorylation-site mutagenesis, ubiquitination assay, siRNA depletion

    PMID:20573420

    Open questions at the time
    • E3 ubiquitin ligase mediating Plk1-dependent degradation not identified
    • Functional consequence of individual phosphorylation sites not dissected
  8. 2011 High

    The physiological importance of PINX1 as a haploinsufficient tumor suppressor was demonstrated: PINX1-null mice are embryonic lethal, and heterozygous mice develop spontaneous tumors with telomerase-dependent chromosomal instability, establishing PINX1 dosage as critical for genome integrity in vivo.

    Evidence Mouse knockout genetics, karyotyping, TRAP, telomere FISH, histopathology

    PMID:21436583

    Open questions at the time
    • Which tissues are most vulnerable to PINX1 haploinsufficiency not fully characterized
    • Whether tumor suppression is solely telomerase-dependent or also involves ribosome biogenesis/DNA repair functions unknown
  9. 2012 Medium

    The cell-cycle dynamics of PINX1 at telomeres were resolved: endogenous PINX1 preferentially associates with telomeres during mitosis (promoting TRF1 accumulation) and mediates hTERT trafficking to telomeres during mid-late S phase, establishing PINX1 as a temporal coordinator of telomerase access.

    Evidence ChIP, immunofluorescence, cell cycle synchronization, siRNA knockdown

    PMID:22331467 PMID:22749911

    Open questions at the time
    • Signals triggering PINX1 telomere association at specific cell-cycle stages not identified
    • Whether PINX1 simultaneously inhibits and recruits telomerase is paradoxical and not resolved
  10. 2014 High

    PINX1 was shown to protect TRF1 from ubiquitin-mediated degradation in an hTERT-dependent manner, with PINX1 loss causing telomeric DNA damage and chromosomal instability; paradoxically, co-depletion of PINX1 and hTERT restores TRF1 stability, revealing a complex regulatory triangle between PINX1, hTERT, and TRF1 at telomeres.

    Evidence Ubiquitination assays, co-IP, siRNA epistasis, γ-H2AX foci, karyotyping

    PMID:24415760

    Open questions at the time
    • Identity of the E3 ligase targeting TRF1 in the absence of PINX1 unknown
    • Structural basis for hTERT-dependent TRF1 stabilization not resolved
  11. 2014 High

    The mechanistic basis of PINX1's ribosome biogenesis function was established at the biochemical level: PINX1's G-patch domain directly binds and stimulates the ATPase activity of Prp43/DHX15, and this interaction is conserved from yeast to human, unifying PINX1's nucleolar role with its molecular activity as a helicase activator.

    Evidence In vitro ATPase assay with purified proteins, G-patch mutagenesis, yeast complementation, co-IP in HeLa cells

    PMID:24823796

    Open questions at the time
    • Specific rRNA or snoRNA substrates remodeled by PINX1-activated DHX15 not identified
    • Whether helicase activation and telomerase inhibition are coordinated or independent unclear
  12. 2014 Medium

    The transcriptional regulation of PINX1 was elucidated: p53 directly activates PINX1 transcription, and HPV16 E6 suppresses it by degrading p53, linking PINX1 expression to the p53 tumor suppressor network.

    Evidence ChIP, luciferase reporter, Western blot, TRAP assay in cervical cancer cells

    PMID:24412852

    Open questions at the time
    • Whether p53-mediated PINX1 induction is the primary mechanism of telomerase repression by p53 not tested
    • Other transcription factors regulating PINX1 under non-stress conditions unknown
  13. 2015 Medium

    PINX1 was found to function as a transcriptional corepressor of ERα, associating with estrogen-responsive promoters and repressing estrogen-mediated proliferation, extending PINX1's role beyond telomere and ribosome functions into nuclear receptor signaling.

    Evidence Co-IP, ChIP on E2-regulated promoters, luciferase reporter, proliferation assays

    PMID:26187699

    Open questions at the time
    • Mechanism of corepressor activity (histone deacetylase recruitment?) not identified
    • Whether corepressor function is relevant in normal breast tissue unknown
  14. 2020 High

    The structural determinants of G-patch–helicase interaction were further refined: PINX1 and Pfa1 bind the Prp43 OB fold through distinct modes, but both require the β4-β5 loop for ATPase stimulation, revealing a shared activation mechanism despite divergent binding.

    Evidence In vitro ATPase/helicase assays with OB-fold mutants, binding assays, yeast genetics

    PMID:32882145

    Open questions at the time
    • Whether PINX1 and Pfa1 compete for Prp43 in vivo or act on different substrate pools not determined
  15. 2024 High

    A telomerase-independent function of PINX1 in DNA damage repair was uncovered: PINX1 binds PARP1's ZnF3-BRCT domain and recruits XRCC1 to damage sites, constitutively promotes PARP1-chromatin association, and its loss sensitizes cells to PARP inhibitors independently of its TID, establishing PINX1 as a bona fide DNA repair factor.

    Evidence IP-mass spectrometry, co-IP domain mapping, ChIP, γ-H2AX/micronucleus assays, PARP inhibitor sensitivity with TID-mutant rescue

    PMID:39174499

    Open questions at the time
    • Whether PINX1 acts in specific repair pathways (BER vs. SSB repair) not fully delineated
    • How PINX1 promotes PARP1-chromatin association mechanistically unknown
    • Relevance to PARP inhibitor response in patient tumors not tested
  16. 2025 High

    PINX1's role in rDNA transcription was established: it directly binds POLR1G and UBTF to promote RNA Pol I preinitiation complex assembly, and nutrient starvation induces acetylation at six lysine residues that blocks POLR1G binding, providing a mechanism for coupling ribosome biogenesis to metabolic state.

    Evidence Co-IP, mass spectrometry for acetylation sites, site-directed mutagenesis, rDNA transcription assays, nutrient starvation

    PMID:40639785

    Open questions at the time
    • Identity of the acetyltransferase and deacetylase controlling PINX1 acetylation unknown
    • Whether acetylation also affects DHX15 activation or telomerase inhibition not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PINX1 coordinates its multiple functions — telomerase inhibition, helicase activation for ribosome biogenesis, rDNA transcription, DNA repair via PARP1, and chromosome segregation — remains unresolved; whether these activities are spatially or temporally segregated and whether they are interdependent or modular is the central open question.
  • No structural model of full-length PINX1 or any of its binary complexes exists
  • Whether PINX1's multiple binding partners compete for overlapping surfaces is untested
  • In vivo separation-of-function mutations distinguishing each role have not been systematically generated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140110 transcription regulator activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-73894 DNA Repair 1
Partners
DHX15NCLNPM1PARP1PLK1POLR1GTERF1TERT
Complex memberships
RNA Pol I preinitiation complex (via POLR1G/UBTF)shelterin-associated complex (via TRF1)telomerase holoenzyme (as inhibitor/regulator)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PinX1 binds directly to the telomerase catalytic subunit hTERT and potently inhibits its activity in vitro; overexpression shortens telomeres and induces crisis, while depletion increases telomerase activity and elongates telomeres. Co-immunoprecipitation, TRAP assay, overexpression and depletion experiments in human cells Cell High 11701125
2001 PinX1 interacts with Pin2/TRF1, and this interaction is mediated by a minimal 20-amino acid sequence of PinX1 and the TRF homology domain of TRF1 via hydrophilic and hydrophobic interactions; disrupting this interaction (Leu-291 mutation in PinX1 or TRF1 knockdown) abolishes PinX1 telomere localization and its ability to inhibit telomere elongation without affecting telomerase activity per se. Deletion analysis, site-directed mutagenesis, RNAi, telomere length assay, co-IP The Journal of biological chemistry High 21119197
2004 PinX1 binds directly to hTERT protein, primarily to its hTR-binding domain; PinX1 also binds hTR, but this association is dependent on hTERT in a cellular context, indicating PinX1 represses telomerase by binding the assembled hTERT·hTR complex. In vitro direct binding assays, co-immunoprecipitation in cells with hTERT-depleted conditions, domain mapping The Journal of biological chemistry High 15381700
2009 PinX1 is a microtubule-binding protein that localizes to nucleoli and telomeres in interphase and relocates to the periphery of chromosomes and the outer plate of kinetochores during mitosis; kinetochore localization requires Hec1 and CENP-E; depletion causes anaphase chromatid bridges and micronuclei, demonstrating a role in faithful chromosome segregation. Deconvolution microscopy, deletion analysis mapping localization domains, siRNA knockdown, real-time imaging, biochemical microtubule-binding assay The Journal of biological chemistry High 19553660
2009 PinX1 is recruited to the chromosome periphery by Nucleolin through its C-terminus; depletion of Nucleolin abolishes chromosomal periphery localization of PinX1, and combined repression of PinX1 and Nucleolin abrogates chromosome segregation. Co-immunoprecipitation, deconvolution microscopy, siRNA depletion, real-time mitosis imaging Biochemical and biophysical research communications Medium 19393617
2009 Silencing PinX1 significantly reduces the association of telomerase with the POT1-containing telomeric protein complex, leading to telomere shortening in telomerase-positive cells but not telomerase-negative cells. shRNA knockdown, co-immunoprecipitation, telomere length analysis (TRF), TRAP assay Cancer research Medium 19117989
2009 PinX1 regulates the nucleolar accumulation of TRF1; nucleolar PinX1 forces endogenous TRF1 into the nucleolus, and nuclear PinX1 enhances TRF1 binding to telomeres; this function is absent in ALT cells, suggesting telomerase dependence. Fluorescence microscopy (co-localization), mutant analysis of localization domains, overexpression experiments in HeLa and ALT cell lines Journal of molecular biology Medium 19265708
2010 The C-terminal fragment of PinX1 (residues 290-328) constitutes the telomerase inhibitory domain (TID) that directly binds hTERT, while residues 254-289 specifically bind Pin2/TRF1; LPTS/PinX1(290-328) shows stronger in vitro telomerase inhibitory activity than full-length protein. Domain deletion mapping, GST pulldown, TRAP assay in vitro, overexpression experiments Biochemical and biophysical research communications Medium 20620128
2010 Polo-like kinase 1 (Plk1) interacts with and phosphorylates PinX1 at five specific sites in vivo and in vitro, promoting its ubiquitin-proteasome-dependent degradation during mitosis; Plk1 depletion increases PinX1 protein stability. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis of phosphorylation sites, siRNA depletion, ubiquitination assay European journal of cell biology High 20573420
2011 Anthracyclines induce ubiquitin-proteasome-dependent degradation of PinX1, disrupting telomerase association with telomeres and impairing telomere maintenance specifically in telomerase-positive cancer cells. Western blotting, co-immunoprecipitation, proteasome inhibitor rescue experiments, telomere FISH Oncogene Medium 21643006
2011 PinX1 heterozygosity activates telomerase and causes telomerase-dependent chromosomal instability in mouse embryonic fibroblasts; PinX1-null mice are embryonic lethal, and PinX1+/- mice spontaneously develop malignant tumors with chromosome instability. Mouse knockout/heterozygous genetics, karyotyping, TRAP assay, telomere FISH, histopathology The Journal of clinical investigation High 21436583
2012 Endogenous PinX1 associates with telomeres primarily at mitosis and is required for TRF1 accumulation on telomeres during mitosis; PinX1 knockdown delays mitotic entry. Chromatin immunoprecipitation (ChIP), immunofluorescence, siRNA knockdown, cell cycle analysis Molecular and cellular biology Medium 22331467
2012 PinX1 mediates the cell cycle-dependent trafficking of hTERT to telomeres during mid-late S phase, and mediates chromosomal localization of hTERT during anaphase. Immunofluorescence, siRNA knockdown, cell cycle-synchronized localization analysis FEBS letters Medium 22749911
2014 PinX1 overexpression stabilizes TRF1 protein and prevents its ubiquitination; PinX1 depletion leads to TRF1 degradation, reduced TRF1 telomere association, DNA damage responses at telomeres, and chromosome instability. hTERT plays dual roles: it is required for PinX1-mediated TRF1 stability in telomerase-positive cells, but paradoxically, co-knockdown of PinX1 and hTERT stabilizes TRF1 and suppresses DNA damage. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, immunofluorescence, DNA damage marker assays, karyotyping The Journal of biological chemistry High 24415760
2014 PINX1 activates the RNA helicase Prp43p/DHX15 via its G-patch domain: PINX1 directly binds yeast Prp43p and stimulates its ATPase activity; mutations of the G-patch abolish complex formation and ATPase stimulation; PINX1 also interacts with human PRP43 (DHX15) in HeLa cells and is required for ribosome biogenesis. In vitro ATPase assay, direct binding assay, G-patch mutagenesis, yeast complementation assay, co-immunoprecipitation in HeLa cells Nucleic acids research High 24823796
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 activities; chromatin immunoprecipitation shows PINX1 associates with ERα on E2-regulated promoters and PINX1 overexpression decreases estrogen-mediated proliferation. Co-immunoprecipitation, ChIP assay, luciferase reporter assay, proliferation assay Molecular and cellular endocrinology Medium 26187699
2015 PinX1 inhibits the migration and invasion of breast cancer cells by suppressing MMP-9 expression and activity via NF-κB-dependent transcription. Cell migration/invasion assay, gelatin zymography, Western blot, NF-κB reporter assay, nude mice metastasis model Molecular cancer Medium 25888829
2017 EV71 viral protease 3C directly interacts with PinX1 and cleaves it at the Q50-G51 site; this cleavage promotes host cell apoptosis and enhances viral release, while PinX1 overexpression reduces apoptosis and viral release. Co-immunoprecipitation, protease cleavage assay with site identification by mutagenesis, overexpression and siRNA knockdown with apoptosis/viral release readouts Journal of virology Medium 27847364
2017 Nucleophosmin (NPM) directly interacts with PinX1; PinX1 acts as a linker between NPM and hTERT, and NPM recruitment by PinX1 to the telomerase complex partially attenuates PinX1-mediated inhibition of telomerase activity. Co-immunoprecipitation, in vitro pulldown, TRAP assay Scientific reports Medium 28255170
2014 PinX1 is a novel target gene of p53; p53 directly activates PinX1 transcription; HPV16 E6 suppresses PinX1 expression by inhibiting p53 transcriptional activity, thereby enhancing telomerase activity in cervical cancer cells. ChIP assay, luciferase reporter assay, Western blot, TRAP assay Biochimica et biophysica acta Medium 24412852
2017 NF-κB p65 directly binds to two consensus response elements in the LPTS/PinX1 promoter (at -1143/-1136 and -888/-881) and suppresses LPTS transcription, thereby promoting cancer cell growth. EMSA, ChIP assay, luciferase reporter with binding site mutations, Western blot, xenograft models Cell communication and signaling Medium 29017500
2019 PinX1 transcriptionally activates miR-125a-3p expression, which in turn inhibits VEGF (its target gene), thereby repressing tumor angiogenesis in renal cell carcinoma. Chromatin immunoprecipitation, luciferase reporter assay, miRNA microarray, in vitro and in vivo angiogenesis assays Angiogenesis Medium 31254127
2019 PinX1 and NPM associate throughout S phase, with NPM/PinX1/hTERT ternary complex formation peaking during early-S phase; PinX1 is required for NPM nucleolar localization during S phase, and long-term co-depletion of PinX1 and NPM causes telomere shortening. Co-immunoprecipitation, immunofluorescence, TRF assay for telomere length, cell cycle synchronization Cell & bioscience Medium 31210926
2020 A novel transcript variant of mPinX1 (mPinX1t) binds to nucleoporin 133 (a nuclear pore complex component), and cells expressing mPinX1t show a higher cytosol-to-nucleus ratio of cardiac transcription factor mRNAs, suggesting mPinX1t positively regulates cardiac differentiation by enhancing mRNA nuclear export. 5'/3' RACE, polysome fractionation, co-immunoprecipitation, Western blot, overexpression/knockdown in ESCs, cardiac differentiation assay Journal of the American Heart Association Medium 32157956
2020 The binding modes of Pfa1 and PINX1 G-patches to Prp43 are distinct: the β4-β5 loop of the Prp43 OB fold is crucial for Pfa1 binding but not essential for PINX1 binding; however, this loop is required for ATPase/helicase stimulation by both activators and is essential for Prp43 function during ribosome biogenesis. In vitro ATPase and helicase assays, domain mutagenesis of Prp43 OB fold, yeast genetic analysis, binding assays RNA biology High 32882145
2024 PINX1 is a PARP1-interacting protein; PINX1 binds the ZnF3-BRCT domain of PARP1, facilitates recruitment of DNA repair factor XRCC1 to DNA lesions, and constitutively promotes PARP1-chromatin association and transcription of DNA repair genes including XRCC1 and GLIS3; PINX1 loss compromises DNA damage repair and renders cells sensitive to PARP inhibitors and etoposide independent of its telomerase inhibitory activity. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, domain binding assays, ChIP, DNA damage assays (γ-H2AX, micronucleus), PARP inhibitor sensitivity assays with full-length and TID-mutant rescue Cell death & disease High 39174499
2025 PinX1 directly binds RNA polymerase I subunit POLR1G (required for RNA Pol I preinitiation complex assembly) together with UBTF, promoting rDNA transcription and ribosome biogenesis; upon nutrient starvation, PinX1 is acetylated at six lysine residues (K43, K133, K140, K149, K190, K222), which hinders its binding to POLR1G and leads to disassembly of the RNA Pol I preinitiation complex. Co-immunoprecipitation, mass spectrometry identification of acetylation sites, site-directed mutagenesis, rDNA transcription assays, ribosome biogenesis assays, nutrient starvation experiments The Journal of biological chemistry High 40639785
2025 PINX1 physically interacts with ILF3 and promotes its ubiquitination via the E3 ubiquitin ligase SPOP, leading to ILF3 degradation; this suppresses the PI3K-AKT-mTOR pathway and inhibits proliferation and cisplatin resistance in NPC cells. Co-immunoprecipitation, immunofluorescence, ubiquitination assay, ChIP, dual-luciferase reporter assay, Western blot American journal of cancer research Medium 40667563
2002 The yeast homolog of PinX1 (Gno1p/YGR280c) is a component of the rRNA processing machinery; its G-patch domain is essential for pre-rRNA processing at sites A0, A1, A2 and for snoRNA 3'-end maturation; human PinX1 can complement the gno1Δ mutation, indicating a conserved role in rRNA maturation. Yeast deletion analysis, rRNA processing assays, mutational analysis of G-patch and KK(E/D) domains, complementation assay The Journal of biological chemistry High 12107183
2004 Human MCRS2, a cell-cycle-dependent protein peaking in early S phase, interacts with LPTS/PinX1 in vitro and in vivo, co-localizes with it in cells, and inhibits telomerase activity in vitro; long-term overexpression of MCRS2 causes telomere shortening. Yeast two-hybrid screening, co-immunoprecipitation, co-localization, in vitro TRAP assay, stable overexpression with telomere length analysis Biochemical and biophysical research communications Medium 15044100
2021 PinX1 acts as an androgen receptor (AR) coactivator in prostate cancer cells, increasing AR transcriptional activity and target gene expression as well as promoting proliferation, migration, and colony formation both in the presence and absence of AR agonist, suggesting an androgen-independent pathway. Luciferase reporter assay, Western blot for AR target genes, proliferation and migration assays in PCa cell lines with PinX1 overexpression/knockdown The Journal of steroid biochemistry and molecular biology Medium 33647521
2024 PinX1 interacts with RBM10, and this interaction may promote telomerase localization to telomeres to facilitate telomere maintenance and inhibit cGAS-STING-mediated immune activation; silencing PinX1 activates the cGAS-STING pathway and enhances radiosensitivity. Immunoprecipitation-mass spectrometry, Western blot, immunofluorescence, cGAS-STING pathway assays, radiosensitivity colony formation assay Journal of translational medicine Low 38431575

Source papers

Stage 0 corpus · 89 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 75 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 48 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 42 24823796
2009 PinX1 is a novel microtubule-binding protein essential for accurate chromosome segregation. The Journal of biological chemistry 42 19553660
2019 PinX1 represses renal cancer angiogenesis via the mir-125a-3p/VEGF signaling pathway. Angiogenesis 37 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
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
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 31 21102596
2012 PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells. Journal of experimental & clinical cancer research : CR 29 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
2009 Human PinX1 mediates TRF1 accumulation in nucleolus and enhances TRF1 binding to telomeres. Journal of molecular biology 21 19265708
2022 Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1. Frontiers in pharmacology 20 35847001
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
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
2010 Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1. Leukemia 19 21102426
2019 Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease. JAMA neurology 17 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
2013 Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells. Oncology reports 16 23912465
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 15 32028978
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
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
2021 PINX1 promotes malignant transformation of thyroid cancer through the activation of the AKT/MAPK/β-catenin signaling pathway. American journal of cancer research 11 34873474
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
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
2024 Silencing PinX1 enhances radiosensitivity and antitumor-immunity of radiotherapy in non-small cell lung cancer. Journal of translational medicine 6 38431575
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
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
2024 PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells. Cell death & disease 3 39174499
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
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
2025 Acetylation of microtubule-binding PinX1 orchestrates ribosome biogenesis to nutrient starvation via the RNA polymerase I preinitiation complex. The Journal of biological chemistry 1 40639785
2022 Inhibition Mechanism of PinX1 Gene on Cancer Stem Cells of Nasopharyngeal Carcinoma. Cellular and molecular biology (Noisy-le-Grand, France) 1 37114251
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