Affinage

TMPO

Lamina-associated polypeptide 2, isoform alpha · UniProt P42166

Round 2 corrected
Length
694 aa
Mass
75.5 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TMPO encodes the LAP2 family of nuclear envelope and nucleoplasmic proteins that function as structural organizers of the nuclear lamina and regulatory scaffolds linking chromatin architecture to cell cycle control, transcription, and differentiation. The integral inner nuclear membrane isoform LAP2β binds lamin B1 and chromosomes in a phosphorylation-regulated manner, recruits BAF via its LEM domain to mediate post-mitotic nuclear envelope reassembly, scaffolds HDAC3 for transcriptional repression, and supports DNA replication initiation through interaction with HA95 and stabilization of Cdc6 (PMID:8324822, PMID:11285238, PMID:12538639, PMID:17364180). The nucleoplasmic isoform LAP2α interacts with A-type lamins and retinoblastoma protein to regulate G1/S progression, nuclear volume, and myogenic differentiation, and cooperates with LAP2β to shuttle the GLI1 transcription factor between the inner nuclear membrane and nucleoplasm via a PKC/acetylation-dependent mechanism (PMID:9382857, PMID:20039368, PMID:30503211). Loss of TMPO protein through autolysosome-dependent degradation activates the ERK/c-Fos/NANOG axis, linking LAP2 stability to cancer stemness and chemoresistance (PMID:38233377).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 High

    The foundational question of how nuclear envelope proteins reassemble after mitosis was addressed by showing LAP2 is an inner nuclear membrane protein that directly binds lamin B1 and chromosomes, with both interactions abolished by mitotic phosphorylation, establishing LAP2 as an early participant in post-mitotic nuclear envelope reformation.

    Evidence In vitro binding assays with purified LAP2 and lamins, phosphorylation by mitotic cytosol, immunofluorescence of dividing HeLa cells

    PMID:8324822

    Open questions at the time
    • Kinase(s) responsible for mitotic phosphorylation not identified at specific sites
    • In vivo consequence of disrupting LAP2–lamin B1 binding not tested
  2. 1997 High

    The question of whether LAP2–lamin interactions have functional consequences beyond structural tethering was answered by showing that the lamin-binding domain of LAP2, when microinjected, blocks nuclear volume increase and G1-to-S progression, establishing LAP2 as a regulator of cell cycle-coupled nuclear growth.

    Evidence Microinjection of recombinant LAP2 domain fragments into HeLa cells, BrdU incorporation and nuclear volume quantification

    PMID:9382857

    Open questions at the time
    • Molecular mechanism linking nuclear lamina dynamics to S-phase entry unresolved
    • Whether effect is specific to LAP2β or shared with LAP2α not determined
  3. 2001 High

    The identity of the chromatin receptor mediating LAP2–chromosome binding was resolved by demonstrating that the LEM domain binds BAF, that BAF·DNA complexes are preferred substrates, and that LEM domain mutations simultaneously disrupt BAF binding and nuclear assembly, establishing the LEM–BAF axis as the molecular bridge between LAP2 and chromatin.

    Evidence Systematic mutagenesis of 17 Xenopus LAP2-c variants, in vitro BAF and BAF·DNA binding assays, Xenopus nuclear assembly extract functional assay

    PMID:11285238

    Open questions at the time
    • Structural basis of LEM–BAF–DNA ternary complex not resolved at this point
    • Contribution of individual LEM residues to in vivo nuclear assembly not tested in mammalian cells
  4. 2003 High

    How LAP2β connects to DNA replication licensing was answered by showing that LAP2β interacts with HA95 and that disruption of this interaction causes proteasome-dependent Cdc6 degradation, blocking replication initiation but not elongation, establishing LAP2β as a scaffold protecting prereplication complex integrity.

    Evidence GST pulldown, immunoprecipitation, in vitro DNA replication assay with purified G1 nuclei and S-phase extract, proteasome inhibitor rescue

    PMID:12538639

    Open questions at the time
    • Direct mechanism by which LAP2β–HA95 interaction prevents Cdc6 degradation unknown
    • Whether LAP2β-dependent Cdc6 stabilization operates genome-wide or at specific replication origins not addressed
  5. 2007 Medium

    The question of whether LAP2β participates in epigenetic regulation was addressed by identifying LAP2β–HDAC3 binding and associated histone H4 deacetylation at the nuclear periphery, linking the nuclear envelope to transcriptional silencing.

    Evidence Co-immunoprecipitation and HDAC activity assays in hematopoietic cell lines

    PMID:17364180

    Open questions at the time
    • Reciprocal validation of LAP2β–HDAC3 interaction not shown
    • Genomic targets of LAP2β-recruited HDAC3-mediated repression not identified
    • Whether HDAC1 also participates at this stage not tested
  6. 2010 High

    The in vivo role of the nucleoplasmic LAP2α isoform was established by showing that LAP2α knockout mice have expanded satellite cell pools and delayed myoblast differentiation, with conditional ablation confirming cell-autonomous functions in muscle remodeling, linking LAP2α–lamin A–Rb complexes to stem cell fate and differentiation.

    Evidence Complete and Cre-conditional LAP2α knockout mice, FACS quantification of satellite cells, in vitro differentiation assays, fiber-type immunostaining

    PMID:20039368

    Open questions at the time
    • Relative contributions of Rb versus lamin A binding to the differentiation phenotype not dissected
    • Whether the expanded stem cell pool reflects altered self-renewal or delayed exit from quiescence unclear
  7. 2018 High

    The question of how nuclear envelope proteins regulate transcription factor availability was answered by demonstrating that LAP2β sequesters acetylated GLI1 at the inner nuclear membrane while LAP2α, scaffolding HDAC1 and regulated by aPKC, deacetylates and releases GLI1 into the nucleoplasm, establishing a cooperative INM-to-nucleoplasm shuttling mechanism for Hedgehog signaling.

    Evidence Co-IP, proximity ligation assay, domain mapping, HDAC1 activity assay, aPKC modulation, GLI1 reporter assays, live imaging in basal cell carcinoma cells

    PMID:30503211

    Open questions at the time
    • Whether this shuttling mechanism applies to transcription factors beyond GLI1 not determined
    • Structural basis of the two-site LAP2β–GLI1 interaction not resolved
  8. 2018 Medium

    A potential link between TMPO dysfunction and metabolic disease was suggested by the finding that heterozygous frameshift TMPO variants that abrogate lamin binding cause LAP2 mislocalization and increased lipid droplet accumulation, associating TMPO with NAFLD susceptibility.

    Evidence Candidate gene sequencing in 37 twin/sibling pairs, co-immunoprecipitation, immunofluorescence, lipid droplet quantification after oleic acid treatment

    PMID:28902428

    Open questions at the time
    • Small cohort size limits genetic confidence
    • Causal mechanism connecting LAP2–lamin disruption to lipid accumulation not defined
    • No animal model confirmation of NAFLD phenotype
  9. 2024 Medium

    The question of how TMPO loss impacts cancer cell behavior was addressed by showing that 5-FU-induced autolysosomal degradation of TMPO activates ERK→c-Fos(Ser374-P)→NANOG transcription, promoting cancer stemness and chemoresistance, positioning TMPO as an upstream suppressor of the ERK/NANOG axis.

    Evidence siRNA knockdown, autophagy/lysosome inhibitors, ChIP of c-Fos at NANOG promoter, phospho-mutant rescue, flow cytometry for stemness markers in colon cancer cells

    PMID:38233377

    Open questions at the time
    • How TMPO degradation activates ERK signaling mechanistically is undefined
    • Whether this pathway operates outside colon cancer contexts unknown
    • Single-lab study awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the LAP2α–lamin A–Rb ternary complex, the genome-wide targets of LAP2β-associated HDAC-mediated silencing, and whether the GLI1 shuttling mechanism represents a general paradigm for transcription factor regulation at the inner nuclear membrane.
  • No high-resolution structure of any LAP2 isoform in complex with lamin or Rb
  • No genome-wide ChIP-seq or DamID for LAP2-dependent gene silencing targets
  • Generality of INM-to-nucleoplasm transcription factor shuttling via LAP2 untested beyond GLI1

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 5 GO:0005635 nuclear envelope 5 GO:0005654 nucleoplasm 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-1266738 Developmental Biology 1 R-HSA-4839726 Chromatin organization 1 R-HSA-69306 DNA Replication 1
Partners
BANF1GLI1HA95HDAC1HDAC3LMNALMNB1RB1

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 LAP2 (encoded by TMPO) is an integral membrane protein of the nuclear envelope that directly binds lamin B1 (but not lamins A/C) and mitotic chromosomes in vitro; mitotic phosphorylation of LAP2 by mitotic cytosol inhibits both its lamin B1 binding and chromosome binding activities. During late anaphase, LAP2 associates with chromosomes prior to assembly of most lamins, suggesting a key role in initial nuclear envelope reassembly events. In vitro binding assays, phosphorylation experiments with mitotic cytosol, immunofluorescence microscopy Cell High 8324822
1995 LAP2 is an integral inner nuclear membrane protein with a large nucleoplasmic domain (residues 1–409) and a single C-terminal transmembrane span (residues 410–433). Multiple regions within the nucleoplasmic domain cooperatively mediate targeting to the nuclear envelope. LAP2 contains several potential cdc2 kinase phosphorylation sites, and its chromosome- and lamin-binding activities are regulated by mitotic phosphorylation. cDNA cloning, deletion mutagenesis expressed in cultured cells, immunogold localization in isolated nuclear envelopes, epitope mapping The EMBO journal High 7737115
1997 Microinjection of the nucleoplasmic domain of LAP2 (residues 1–398) into metaphase HeLa cells does not block nuclear reassembly but strongly inhibits nuclear volume increase. This effect is specifically due to the lamin-binding region of LAP2 (residues 298–373), not the chromatin-binding domain (residues 1–88). Injection of the lamin-binding fragment during early G1 phase prevents the ~3-fold nuclear volume increase and almost completely blocks entry into S phase, whereas injection during S phase has no effect on ongoing DNA replication. These results indicate that LAP2 regulates nuclear lamina dynamics required for nuclear growth and G1-to-S progression. Microinjection of recombinant LAP2 domain polypeptides into HeLa cells, time-lapse imaging of nuclear volume, BrdU incorporation assay for S-phase entry The Journal of cell biology High 9382857
1998 During spermiogenesis, LAP2/thymopoietin isoforms (TPβ/LAP2, TPγ, TPα) show coordinated and differential expression and localization: TPγ disappears first, then LAP2/TPβ, with only TPα detectable in mature sperm. LAP2 localization shifts progressively from the full nuclear periphery to one spot at the centriolar pole of spermatid nuclei, mirroring the behavior of lamin B1, demonstrating that LAP2 and lamins are coordinately regulated during a differentiation process. Immunofluorescence microscopy with isoform-specific antibodies during rat spermiogenesis, Western blotting Journal of cell science Medium 9664044
1999 L2BP1 (LAP2 binding protein 1, the rat homolog of BAF/Barrier-to-Autointegration Factor) directly interacts with LAP2. L2BP1/BAF is distributed diffusely throughout the nucleus during interphase but concentrates on chromosomes during M-phase. The L2BP1-binding domain of LAP2 overlaps with LAP2's chromosome-binding region, indicating that BAF is a candidate mediator of LAP2–chromosome interaction at the end of mitosis. Yeast two-hybrid identification, cDNA cloning, immunofluorescence localization in dividing cells, domain mapping Journal of cell science Medium 10393804
2001 The LEM domain of LAP2 is the core binding domain for BAF (Barrier-to-Autointegration Factor). LAP2 binds BAF·DNA complexes with higher affinity than BAF alone, suggesting BAF changes conformation upon DNA binding. The nucleoplasmic domains of Xenopus LAP2 isoforms vary ~9-fold in affinity for BAF but all supershift BAF·DNA complexes. LAP2-c (N-terminal constant region containing LEM domain) inhibits nuclear assembly in Xenopus extracts, and LEM domain mutations simultaneously disrupt BAF binding and nuclear assembly inhibition. Systematic mutagenesis (17 Xenopus LAP2-c mutants), in vitro binding assays with purified BAF and BAF·DNA complexes, Xenopus nuclear assembly extract assay, gel shift (supershift) assay The EMBO journal High 11285238
2003 LAP2β interacts with the chromatin-associated protein HA95 through two binding regions: residues 137–242 and residues 299–373 (which overlaps the lamin B-binding domain). Disruption of HA95 binding to the N-terminal LAP2β domain (residues 137–242) abolishes initiation of DNA replication in purified G1-phase nuclei incubated in S-phase extract, without affecting elongation. This replication block correlates with proteasome-mediated degradation of Cdc6 (a prereplication complex component), which is rescued by proteasome inhibitors, restoring replication. GST pulldown, protein overlay assay, immunoprecipitation, in vitro DNA replication assay using purified G1-phase nuclei and S-phase extract, proteasome inhibitor rescue The Journal of cell biology High 12538639
2007 LAP2β binds histone deacetylase 3 (HDAC3), resulting in histone H4 deacetylation. This LAP2β–HDAC3 interaction at the nuclear envelope is implicated in transcriptional repression, and LAP2β expression is strongly upregulated in highly proliferative normal and malignant hematopoietic cells. Co-immunoprecipitation, histone deacetylase activity assays, immunohistochemistry and Western blotting in hematological malignancy cell lines Annals of hematology Medium 17364180
2010 LAP2α (a nucleoplasmic isoform encoded by TMPO) interacts with A-type lamins and the retinoblastoma protein (Rb) to regulate cell cycle progression. Loss of LAP2α in knockout mice increases the satellite cell pool and delays myoblast differentiation in vitro. LAP2α also influences fiber-type ratios in adult slow muscles, shifting them toward fast fiber types. Conditional muscle-specific ablation recapitulates early differentiation defects and fiber-type alterations without changing stem cell numbers, demonstrating cell-autonomous roles of LAP2α in myogenic differentiation and muscle remodeling. Complete and conditional (Cre-mediated) LAP2α knockout mice, in vitro myoblast differentiation assays, fiber-type immunostaining, satellite cell quantification by FACS Stem cells (Dayton, Ohio) High 20039368
2012 LAP2β (encoded by TMPO) is widely overexpressed in digestive tract cancers and regulates cancer cell motility. Knockdown of LAP2β decreases migration and invasion of multiple cancer cell lines and reduces hepatic metastasis in a xenograft model; overexpression increases motility. cDNA microarray analysis suggests MARCKS and IL-6 as potential downstream mediators of LAP2β-regulated motility. Immunohistochemistry in patient tissues, siRNA knockdown, Boyden chamber and wound-healing assays, Matrigel invasion, liver metastasis xenograft model, cDNA microarray PloS one Medium 22745766
2015 The LAP2α-specific isoform of TMPO arose in mammals through co-option of a DIRS1-like retrotransposon element that was alternatively spliced into the TMPO locus, creating a new protein domain (the LAP2α domain). This retrotransposon domestication event occurred separately from a similar event in ZNF451. The alternative splicing of the retrotransposed sequence allowed production of both the new LAP2α isoform and the original shorter isoform, and LAP2α is evolving under strong purifying selection, consistent with an important cellular function. Comparative genomics, sequence similarity analysis across vertebrate lineages, evolutionary rate analysis (dN/dS), alignment of LAP2α domains to repetitive elements Bioinformatics (Oxford, England) Low 25735770
2018 LAP2 isoforms regulate GLI1 transcription factor nuclear trafficking in basal cell carcinomas via a two-site mechanism: LAP2β on the inner nuclear membrane (INM) forms a two-site interaction with the GLI1 zinc-finger domain and acetylation site, stabilizing an acetylation-dependent GLI1 reserve on the INM. Nucleoplasmic LAP2α competes with LAP2β for GLI1 while simultaneously scaffolding HDAC1 to deacetylate GLI1's secondary binding site. Atypical protein kinase Cι/λ (aPKC) promotes GLI1 association with LAP2α, driving GLI1 egress off the INM and enabling maximal Hedgehog pathway output. Co-immunoprecipitation, proximity ligation assay, domain mapping, HDAC1 activity assays, aPKC kinase activity modulation, siRNA knockdown of LAP2 isoforms, GLI1 reporter assays, live imaging of GLI1 nuclear movement Cell High 30503211
2018 Heterozygous frameshift variants in TMPO (generating truncated LAP2 protein) are associated with NAFLD in twins/siblings. A truncated LAP2 variant abrogates lamin–LAP2 binding, causes LAP2 mislocalization, alters endogenous lamin distribution, increases lipid droplet accumulation after oleic acid treatment, and leads to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1 in transfected cells. Candidate gene sequencing in 37 twin/sibling pairs, co-immunoprecipitation, immunofluorescence microscopy, lipid droplet staining after oleic acid treatment, Western blotting Hepatology (Baltimore, Md.) Medium 28902428
2024 5-FU treatment induces autolysosome-dependent degradation of TMPO protein, which subsequently triggers ERK-mediated phosphorylation of c-Fos. Phosphorylated c-Fos binds the NANOG promoter (requiring Ser374 phosphorylation), promoting NANOG transcription and cancer stem cell properties that confer 5-FU resistance in colon cancer cells. TMPO thus acts upstream of the ERK/c-Fos/NANOG axis to regulate chemoresistance. siRNA knockdown, autophagy/lysosome inhibitors, Western blotting, ChIP assay (c-Fos binding NANOG promoter), c-Fos phospho-mutant rescue experiments, flow cytometry for stemness markers Cell death & disease Medium 38233377
2006 Mass spectrometric phosphoproteomics of HeLa cells identified multiple phosphorylation sites on TMPO/LAP2 protein, confirming it as a phosphoprotein regulated during EGF signaling and general cell signaling contexts. Large-scale phosphoproteomics by mass spectrometry (strong cation exchange + LC-MS/MS) of HeLa cell nuclear fraction and whole-cell lysates Cell Low 15302935 17081983

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. The Journal of cell biology 1850 22412018
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1993 Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell 488 8324822
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2014 Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America 436 24927568
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. The EMBO journal 362 25796446
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2013 Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor. Cell reports 307 23403292
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2018 Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation. Cell reports 274 30110629
2011 A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 269 21654808
1999 LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction. Journal of cell science 195 10393804
2001 LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by variable regions. The EMBO journal 179 11285238
2022 Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer. Journal of nanobiotechnology 169 35078498
1995 Cloning of a cDNA for lamina-associated polypeptide 2 (LAP2) and identification of regions that specify targeting to the nuclear envelope. The EMBO journal 167 7737115
1994 Hepadnavirus P protein utilizes a tyrosine residue in the TP domain to prime reverse transcription. Journal of virology 135 7512155
2012 Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrobial agents and chemotherapy 127 22354310
2009 Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP receptors. British journal of pharmacology 126 19154435
2018 TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma. Oncotarget 105 29719619
1997 Lamin-binding fragment of LAP2 inhibits increase in nuclear volume during the cell cycle and progression into S phase. The Journal of cell biology 98 9382857
1997 Transcomplementation of nucleotide priming and reverse transcription between independently expressed TP and RT domains of the hepatitis B virus reverse transcriptase. Journal of virology 91 9060659
2001 Simultaneous and functional binding of SmpB and EF-Tu-TP to the alanyl acceptor arm of tmRNA. Journal of molecular biology 90 11724528
2007 S/P and T/P phosphorylation is critical for tau neurotoxicity in Drosophila. Journal of neuroscience research 86 17335084
2007 Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochimica et biophysica acta 86 17499021
2005 Cloning and characterization of the goadsporin biosynthetic gene cluster from Streptomyces sp. TP-A0584. Microbiology (Reading, England) 73 16339937
2001 Prostanoid EP(1)- and TP-receptors involved in the contraction of human pulmonary veins. British journal of pharmacology 63 11739243
2000 TP receptor-mediated vasoconstriction in microperfused afferent arterioles: roles of O(2)(-) and NO. American journal of physiology. Renal physiology 61 10919850
1998 Nuclear envelope remodelling during rat spermiogenesis: distribution and expression pattern of LAP2/thymopoietins. Journal of cell science 61 9664044
2003 HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication. The Journal of cell biology 60 12538639
2018 LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription. Cell 53 30503211
2005 S18886, a selective TP receptor antagonist, inhibits development of atherosclerosis in rabbits. Atherosclerosis 52 15950232
2019 ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression. Molecular and cellular biology 50 31501276
2014 Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events. The European respiratory journal 47 25323233
2010 Isolation and characterization of the gene cluster for biosynthesis of the thiopeptide antibiotic TP-1161. Applied and environmental microbiology 47 20851988
2002 Angiogenic co-operation of VEGF and stromal cell TP in endometrial carcinomas. The Journal of pathology 47 11920737
2010 The thromboxane/endoperoxide receptor (TP): the common villain. Journal of cardiovascular pharmacology 46 20422736
2009 TP receptor antagonism: a new concept in atherothrombosis and stroke prevention. Cerebrovascular diseases (Basel, Switzerland) 44 19439937
2010 Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber-type determination. Stem cells (Dayton, Ohio) 43 20039368
2010 PC-TP/StARD2: Of membranes and metabolism. Trends in endocrinology and metabolism: TEM 42 20338778
2014 Prostaglandin I2 and prostaglandin E2 modulate human intrarenal artery contractility through prostaglandin E2-EP4, prostacyclin-IP, and thromboxane A2-TP receptors. Hypertension (Dallas, Tex. : 1979) 39 24914192
1990 EP3, but not EP2, FP, or TP prostanoid-receptor stimulation may reduce intraocular pressure. Investigative ophthalmology & visual science 38 2176184
2021 Long noncoding RNA TMPO-AS1/miR-126-5p/BRCC3 axis accelerates gastric cancer progression and angiogenesis via activating PI3K/Akt/mTOR pathway. Journal of gastroenterology and hepatology 37 33295056
2019 Antimalarial Drug Pyrimethamine Plays a Dual Role in Antitumor Proliferation and Metastasis through Targeting DHFR and TP. Molecular cancer therapeutics 37 30642883
2019 TMPO-AS1 promotes cervical cancer progression by upregulating RAB14 via sponging miR-577. The journal of gene medicine 37 31483914
2010 Prostanoid and TP-receptors in atherothrombosis: is there a role for their antagonism? Thrombosis and haemostasis 37 20886180
2013 Terutroban, a TP-receptor antagonist, reduces portal pressure in cirrhotic rats. Hepatology (Baltimore, Md.) 35 23703868
2020 Long noncoding RNA TMPO-AS1 promotes lung adenocarcinoma progression and is negatively regulated by miR-383-5p. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 32062549
2020 Proliferation-associated long noncoding RNA, TMPO-AS1, is a potential therapeutic target for triple-negative breast cancer. Cancer science 31 32437068
2017 TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy. European journal of pharmacology 31 29154838
2015 Alternative splicing and co-option of transposable elements: the case of TMPO/LAP2α and ZNF451 in mammals. Bioinformatics (Oxford, England) 30 25735770
2020 TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer. The international journal of biochemistry & cell biology 29 32087328
2006 Thromboxane hypersensitivity in hypoxic pulmonary artery myocytes: altered TP receptor localization and kinetics. American journal of physiology. Lung cellular and molecular physiology 29 17085527
2022 LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription. Experimental & molecular medicine 27 35760875
2021 AXL Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer. Molecular cancer therapeutics 27 34675118
2024 c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer. Cell death & disease 26 38233377
2012 LAP2 is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. PloS one 26 22745766
2005 Brain prostanoid TP receptor-mediated adrenal noradrenaline secretion and EP3 receptor-mediated sympathetic noradrenaline release in rats. European journal of pharmacology 26 15814087
2016 Tumor Protein (TP)-p53 Members as Regulators of Autophagy in Tumor Cells upon Marine Drug Exposure. Marine drugs 25 27537898
2003 Cloning and characterization of a gene encoding trehalose phosphorylase (TP) from Pleurotus sajor-caju. Protein expression and purification 25 12880768
2021 Mutual Promotion of LAP2 and CAT2 Synergistically Regulates Plant Salt and Osmotic Stress Tolerance. Frontiers in plant science 24 34177987
2020 LncRNA TMPO-AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32692467
2014 Involvement of the TP receptor in TNF-α-induced endothelial tissue factor expression. Vascular pharmacology 24 24699252
2021 Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models. Leukemia 23 34741118
2014 Evaluation of Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 23 24481092
2010 TP receptor activation and inhibition in atherothrombosis: the paradigm of diabetes mellitus. Internal and emergency medicine 23 20734162
2019 Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors. Antioxidants (Basel, Switzerland) 22 31234522
2020 Overexpression and Clinicopathological Correlation of Long Noncoding RNA TMPO-AS1 in Colorectal Cancer Patients. Journal of gastrointestinal cancer 21 31768869
2018 Sequence, genome organization, annotation and proteomics of the thermophilic, 47.7-kb Geobacillus stearothermophilus bacteriophage TP-84 and its classification in the new Tp84virus genus. PloS one 21 29624616
2007 A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells. Bioscience, biotechnology, and biochemistry 21 17420589
2020 LncRNA TMPO-AS1 up-regulates the expression of HIF-1α and promotes the malignant phenotypes of retinoblastoma cells via sponging miR-199a-5p. Pathology, research and practice 20 32139259
2018 Demethoxycurcumin sensitizes the response of non-small cell lung cancer to cisplatin through downregulation of TP and ERCC1-related pathways. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 30668408
2016 Vascular hepoxilin and trioxilins mediate vasorelaxation through TP receptor inhibition in mouse arteries. Acta physiologica (Oxford, England) 20 26666460
2011 The Arabidopsis aminopeptidase LAP2 regulates plant growth, leaf longevity and stress response. The New phytologist 20 21569035
2007 Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. Annals of hematology 20 17364180
2007 Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice. American journal of physiology. Renal physiology 20 17942572
2021 Prevalence of TP-53/Rb-1 Co-Mutation in Large Cell Neuroendocrine Carcinoma. Frontiers in oncology 19 34141612
2018 Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.) 19 28902428
2018 PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway. Cancer biology & therapy 19 29370570
2014 Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis. Modern rheumatology 19 24593208
2021 Long non-coding RNA TMPO-AS1 facilitates chemoresistance and invasion in breast cancer by modulating the miR-1179/TRIM37 axis. Oncology letters 18 33981362
2020 Roles of a TMPO-AS1/microRNA-200c/TMEFF2 ceRNA network in the malignant behaviors and 5-FU resistance of ovarian cancer cells. Experimental and molecular pathology 18 32497621
2002 Differential peristaltic motor effects of prostanoid (DP, EP, IP, TP) and leukotriene receptor agonists in the guinea-pig isolated small intestine. British journal of pharmacology 18 12429577
2021 The Long Non-coding RNA TMPO-AS1 Promotes Bladder Cancer Growth and Progression via OTUB1-Induced E2F1 Deubiquitination. Frontiers in oncology 17 33816295
2023 The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/β-catenin signaling. Cell death discovery 16 37542040
2021 Long non-coding RNA TMPO-AS1 facilitates the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression. Journal of gastroenterology and hepatology 16 34370878
2020 Propofol suppresses hypoxia-induced esophageal cancer cell migration, invasion, and EMT through regulating lncRNA TMPO-AS1/miR-498 axis. Thoracic cancer 16 32643321
2024 Mesenchymal-epithelial transition and AXL inhibitor TP-0903 sensitise triple-negative breast cancer cells to the antimalarial compound, artesunate. Scientific reports 14 38172210
2023 Trial of thromboxane receptor inhibition with ifetroban: TP receptors regulate eicosanoid homeostasis in aspirin-exacerbated respiratory disease. The Journal of allergy and clinical immunology 14 37068712
2022 Histone arginine methyltransferase CARM1 selective inhibitor TP-064 induces apoptosis in endometrial cancer. Biochemical and biophysical research communications 14 35245741
2022 Cloning and Characterization of a Thermostable Endolysin of Bacteriophage TP-84 as a Potential Disinfectant and Biofilm-Removing Biological Agent. International journal of molecular sciences 14 35886960
2021 Docosahexaenoic acid inhibits U46619- and prostaglandin F2α-induced pig coronary and basilar artery contractions by inhibiting prostanoid TP receptors. European journal of pharmacology 14 34329614
2020 LncRNA TMPO-AS1 facilitates the proliferation and metastasis of NSCLC cells by up-regulating ERBB2 via sponging miR-204-3p. International journal of immunopathology and pharmacology 14 32969763
2014 Transcriptional regulation of miR-146b by C/EBPβ LAP2 in esophageal cancer cells. Biochemical and biophysical research communications 14 24589738
2023 Thromboxane A2-TP axis promotes adipose tissue macrophages M1 polarization leading to insulin resistance in obesity. Biochemical pharmacology 13 36849064
2023 Thymopentin (TP-5) prevents lipopolysaccharide-induced neuroinflammation and dopaminergic neuron injury by inhibiting the NF-κB/NLRP3 signaling pathway. International immunopharmacology 13 37121113
2013 Antagonising EP1 and EP2 receptors reveal that the TP receptor mediates a component of antigen-induced contraction of the guinea pig trachea. European journal of pharmacology 13 24012781
2004 Increased expression of thymidine phosphorylase in tumor tissue in proportion to TP-expression in primary normal tissue. Oncology reports 13 15289834
1995 Pharmacokinetics and pharmacodynamics of TP-9201, a GPIIbIIIa antagonist, in rats and dogs. Journal of cardiovascular pharmacology 13 7564333
2021 Down-Regulation of TMPO-AS1 Induces Apoptosis in Lung Carcinoma Cells by Regulating miR-143-3p/CDK1 Axis. Technology in cancer research & treatment 12 33685293
2020 TMPO-AS1 promotes cell proliferation of thyroid cancer via sponging miR-498 to modulate TMPO. Cancer cell international 12 32669970
2020 Prostacyclin facilitates vascular smooth muscle cell phenotypic transformation via activating TP receptors when IP receptors are deficient. Acta physiologica (Oxford, England) 12 32886850
2022 Investigations on the Wound Healing Potential of Tilapia Piscidin (TP)2-5 and TP2-6. Marine drugs 11 35323503
2021 Long non-coding RNA TMPO-AS1 serves as a tumor promoter in pancreatic carcinoma by regulating miR-383-5p/SOX11. Oncology letters 11 33664819
2021 PRMT4 inhibitor TP-064 impacts both inflammatory and metabolic processes without changing the susceptibility for early atherosclerotic lesions in male apolipoprotein E knockout mice. Atherosclerosis 11 34785428
2020 LncRNA-TMPO-AS1 promotes apoptosis of osteosarcoma cells by targeting miR-329 and regulating E2F1. European review for medical and pharmacological sciences 11 33215415
2020 LncRNA TMPO-AS1 Promotes Proliferation and Invasion by Sponging miR-383-5p in Glioma Cells. Cancer management and research 11 33262650
2020 Larger endothelium-dependent contractions in iliac arteries of adult SHRs are attributed to differential downregulation of TP and EP3 receptors in the vessels of WKYs and SHRs during the transition from adolescence to adulthood. European journal of pharmacology 11 33347824
2019 Heteromerization fingerprints between bradykinin B2 and thromboxane TP receptors in native cells. PloS one 11 31086419
2012 Laropiprant attenuates EP3 and TP prostanoid receptor-mediated thrombus formation. PloS one 11 22870195
2011 Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element. Gene therapy 11 22089494
2004 Thromboxane A2 (TP) receptor in the non-pregnant porcine myometrium and its role in regulation of spontaneous contractile activity. European journal of pharmacology 11 14757156