Nucleoprotein TPR · UniProt P12270
TPR is a large coiled-coil nucleoporin that constitutes the intranuclear filaments anchored to the nucleoplasmic face of the nuclear pore complex (NPC), where it serves as a multifunctional scaffold of the nuclear basket (PMID:9024684, PMID:7798308). It is recruited to the NPC through N-terminal heptad-repeat coiled-coil segments while its acidic C-terminal domain carries the nuclear localization signal that directs its own importin alpha/beta-mediated import (PMID:9864356, PMID:9828100, PMID:19835572). Anchored at the basket, TPR organizes nucleocytoplasmic transport: it is required for nuclear export of leucine-rich NES-bearing proteins (PMID:11839768) and operates as an integral component of the TREX-2/NXF1 mRNA export pathway, where its loss disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) with NPCs and traps short, intron-poor transcripts in nuclear speckles downstream of NXF1 recruitment (PMID:32917881, PMID:33091126); TPR conversely restrains export of intron-retaining transcripts trafficking through the NXF1/NXT1 pathway, an activity dependent on Nup153-mediated NPC docking (PMID:21613532, PMID:22253824). TPR also governs mitotic fidelity through the spindle assembly checkpoint: it directly binds and stabilizes Mad1 and Mad2, maintaining their NPC and kinetochore localization and the Mad1-cMad2 pool needed for robust APC/Cdc20 inhibition (PMID:18981471, PMID:24344181), a function gated by CDK1 phosphorylation of Ser2059 that is required for the TPR–Mad1 interaction (PMID:24938596). Beyond transport and checkpoint roles, TPR acts as both substrate and scaffold for ERK2, binding it through a DEF docking motif and promoting ERK2 nuclear translocation (PMID:18794356), and scaffolds an ERK-dependent phosphorylation of Nup153 that negatively regulates NPC biogenesis (PMID:30228202). TPR additionally associates with lamin B1 to organize the nuclear lamina and NPC distribution (PMID:30762072) and protects genome stability by preventing transcription-associated replication stress and DNA-RNA hybrid accumulation (PMID:34168151). The N-terminal coiled-coil region of TPR is recurrently captured in oncogenic kinase fusions including TPR-MET, providing a dimerization domain that yields a constitutively active, autophosphorylating tyrosine kinase that signals through Grb2/Shc to transform cells (PMID:7798308, PMID:3277171, PMID:7838524, PMID:8662733).
Establishing the primary structure of TPR was the prerequisite for understanding both its scaffolding and its oncogenic-fusion roles.
Evidence cDNA cloning and sequencing of the human gene with structural prediction
Characterizing the TPR-MET fusion product answered how a TPR rearrangement causes transformation, showing TPR contributes a constitutively activating module to a tyrosine kinase.
Evidence Immunocomplex kinase assays and in vivo phosphorylation analysis of p65tpr-met
Mapping the signaling requirements of TPR-MET defined which effector couplings drive transformation.
Evidence Site-directed Tyr489 mutagenesis with fibroblast transformation and Co-IP of signaling proteins
Resolving TPR's localization to the nucleoplasmic side of the NPC established it as a nuclear basket component rather than a cytoplasmic filament protein, redirecting functional hypotheses.
Evidence Reciprocal immunoelectron microscopy with multiple epitope antibodies across vertebrate species
Domain dissection separated TPR's NPC-anchoring and self-import determinants and provided the first functional link to mRNA export.
Evidence Deletion/chimeric constructs with poly(A)+ RNA FISH and importin Co-IP in mammalian cells and Xenopus extracts
PMID:9531546 PMID:9828100 PMID:9864356
Functional perturbation distinguished TPR's role in protein/RNA export from import, refining its transport function.
Evidence Antibody microinjection in mitotic and interphase cells with NES-export versus NLS-import readouts and poly(A)+ FISH
Discovery of direct Mad1/Mad2 binding and ERK2 scaffolding assigned TPR mitotic-checkpoint and MAPK-signaling functions beyond transport.
Evidence Affinity-purification MS, direct binding assays, siRNA with checkpoint readouts, and in vitro ERK2 kinase/translocation assays
Demonstrating that TPR stabilizes Mad1/Mad2 proteostasis clarified the mechanism by which it sustains SAC robustness.
Evidence Co-IP, protein half-life measurements, siRNA with GFP-Mad2 rescue and kinetochore imaging
Identifying CDK1 phosphorylation of Ser2059 provided a cell-cycle switch controlling the TPR-Mad1 interaction.
Evidence MS phosphosite mapping, in vitro CDK1/PKA kinase assays, phospho-mutant Co-IP and imaging
Acute degron depletion revealed TPR as a negative regulator of NPC number acting through ERK-mediated Nup153 phosphorylation.
Evidence Auxin-inducible degron depletion, NPC counting, kinase inhibition and phospho/Co-IP assays
Acute depletion plus transcriptomics placed TPR as an integral TREX-2/NXF1 export factor required for short, intron-poor transcripts to exit nuclear speckles.
Evidence AID depletion, nuclear/cytoplasmic RNA-seq, TREX-2 NPC-association assays and speckle co-localization
Linking TPR loss to replication stress and DNA-RNA hybrids connected its export/processing scaffolding to genome stability.
Evidence DNA fiber assays, EM of replication intermediates, proteomic interaction screen (MATR3, SUGP2, GANP) and functional validation
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1997 | Tpr (p270) is a constitutive component of the intranuclear filaments attached to the nucleoplasmic annulus of the nuclear pore complex (NPC) in vertebrate cells, localized exclusively on the nucleoplasmic side, not the cytoplasmic surface. | Immunoelectron microscopy with multiple antibodies against different Tpr epitopes in mammalian and amphibian cells | The Journal of cell biology | High | 9024684 |
| 1994 | Tpr is a large (~265 kDa) coiled-coil protein and a component of the nuclear pore complex; its amino-terminal region is the portion incorporated into oncogenic kinase fusions (TPR-MET, TPR-TRK, TPR-RAF). Tpr is assembled into NPCs later than O-glycosylated nucleoporins during post-mitotic NPC reassembly. | Monoclonal antibody immunofluorescence and immunogold EM; in vitro translation; peptide sequencing from rat liver NEs | The Journal of cell biology | High | 7798308 |
| 1998 | Tpr (via its N-terminal coiled-coil domain) associates with the nuclear basket of the NPC; its acidic C-terminal domain contains a nuclear localization signal and can mediate nuclear import. Ectopic expression of full-length Tpr or NPC-associated domains causes accumulation of poly(A)+ RNA in the nucleus, implicating Tpr in mRNA export. | Mammalian cell transfection with full-length and deletion mutant constructs; fluorescence microscopy; poly(A)+ RNA in situ hybridization | The Journal of cell biology | Medium | 9864356 |
| 1998 | Tpr forms stable subcomplexes with importin alpha and importin beta in Xenopus egg extracts (and in assembled nuclear pores), making it a major physiological binding site for importin beta. Unlike Nup153, Tpr binds importin beta/alpha heterodimers only when they are NOT carrying an NLS substrate, and the complex is disassembled by GMP-PNP. | Immunoprecipitation from Xenopus egg extracts and isolated nuclei; solid-phase binding; immunofluorescence localization | The Journal of cell biology | High | 9531546 |
| 2002 | Tpr is concentrated within the nuclear basket of the NPC (not in long intranuclear filaments). Antibody-mediated depletion of Tpr from NPC (by injection into mitotic cells) did not affect nuclear import mediated by a basic NLS, but significantly retarded nuclear export mediated by a leucine-rich NES signal. Intra-nuclear injection of anti-Tpr antibodies in interphase cells similarly inhibited protein export but not import. | Antibody microinjection into mitotic and interphase cells; GFP-Tpr live imaging; immunofluorescence; EM immunolocalization | The Journal of cell biology | High | 11839768 |
| 2001 | TPR directly binds Nup98 in vitro, and via Nup98 also associates with Nup96. TPR colocalizes with Nup98 in a characteristic intranuclear filamentous network extending from NPCs toward the nucleolus. | In vitro translated protein binding assay; double immunofluorescence microscopy; overexpression of myc-tagged pyruvate kinase-6kDa fusion; double-immunoelectron microscopy | Proceedings of the National Academy of Sciences of the United States of America | Medium | 11248057 |
| 2002 | Tpr is required for normal intranuclear dynamics of RNA Pol II transcripts, including processing, intranuclear transport, and export of poly(A)+ RNA; depletion causes accumulation of poly(A)+ RNA in enlarged SC35-positive nuclear speckles, without affecting NLS-mediated import or NES-mediated export. | Antibody microinjection into mammalian interphase cells; poly(A)+ RNA FISH; immunofluorescence | Genes to cells | Medium | 11952838 |
| 2008 | ERK2 directly phosphorylates Tpr and binds to a DEF (FXF) docking domain on Tpr. ERK2 phosphorylation and dimerization are both required for stable ERK2-Tpr binding, and phosphorylation of Tpr positively cooperates with the DEF domain to promote this binding (unlike most substrates). Ectopic expression or depletion of Tpr decreases movement of activated ERK2 from cytoplasm to nucleus, indicating Tpr functions as both substrate and scaffold for ERK2. | In vitro kinase assays; mutagenesis of phosphorylation sites and DEF domain; co-immunoprecipitation; cell fractionation; ERK2 nuclear translocation assays | Molecular and cellular biology | High | 18794356 |
| 2008 | Tpr directly binds Mad1 and Mad2 at the NPC during interphase. Depletion of Tpr in HeLa cells disrupts NPC localization of Mad1 and Mad2 during interphase, decreases Mad1-bound Mad2 levels, and reduces Mad1 at kinetochores during prometaphase, resulting in failure to activate Mad2 and inhibit APC/Cdc20—implicating Tpr in spindle assembly checkpoint signaling. | Mass spectrometry of affinity-purified Mad2-associated factors; direct binding assays; siRNA knockdown; immunofluorescence of kinetochore proteins | Genes & development | High | 18981471 |
| 2010 | Tpr associates with the molecular motors dynein and dynactin, and with spindle checkpoint proteins Mad1 and Mad2 during cell division. Tpr overexpression causes multinucleated cell formation; knockdown causes lagging chromosome phenotype and disrupts spindle checkpoint protein localization. Rescue and dominant-negative experiments confirm that Tpr orchestrates proper chromosome segregation through interaction with dynein light chain. | Co-immunoprecipitation; RNAi knockdown; overexpression; rescue experiments; immunofluorescence | The Journal of biological chemistry | Medium | 20133940 |
| 2011 | Tpr regulates export of mRNAs with retained introns that traffic through the Nxf1/Nxt1 pathway. Modest knockdown of Tpr by RNAi significantly increases export and translation of mRNA containing a CTE (Constitutive Transport Element), but has no effect on CRM1/Rev-RRE-dependent export or fully spliced mRNA export. | RNAi knockdown; reporter constructs with CTE vs. RRE elements; cytoplasmic/nuclear RNA quantification | RNA | Medium | 21613532 |
| 2012 | Localization of Tpr to the NPC (dependent on Nup153) is necessary for its function in regulating unspliced RNA export. Tpr knockdown dramatically enhances export of CTE-containing unspliced RNA, an effect independent of Sam68 and Tap/Nxf1 but dependent on Nup153 co-action. | siRNA knockdown; Gag/Pol-CTE reporter assay; rescue with siRNA-resistant Tpr; fractionation | PloS one | Medium | 22253824 |
| 2013 | Tpr stabilizes Mad1 and Mad2 proteins (forms a Tpr/Mad1/Mad2 complex) during interphase and mitosis, and is required for normal SAC response by maintaining Mad1-cMad2 levels. Tpr is required for Mad2 (but not Mad1) kinetochore localization; SAC robustness depends on Mad2 levels at kinetochores. Mechanistically, Tpr may spatially regulate SAC proteostasis through SUMO-isopeptidases SENP1 and SENP2 at NPCs. | Co-immunoprecipitation (Tpr with Mad1/Mad2); protein half-life measurements; siRNA depletion; GFP-Mad2 rescue; immunofluorescence | The Journal of cell biology | High | 24344181 |
| 2014 | Tpr is phosphorylated at S2059 by CDK1 during mitosis, causing distinct chromatin localization in telophase. Phosphorylation at S2094 by protein kinase A is hyperphosphorylated during mitosis. Abrogation of S2059 phosphorylation abolishes Tpr-Mad1 interaction and disrupts Mad1/Mad2 localization, causing cell cycle defects. | Mass spectrometry identification of phosphosites; in vitro kinase assays with CDK1 and PKA; phospho-mutant analysis; Co-IP; immunofluorescence | Journal of cell science | High | 24938596 |
| 2018 | Depletion of Tpr (but not Nup153) dramatically increases the total NPC number in various cell types. This negative regulation operates through a phosphorylation cascade: ERK (MAPK) phosphorylates Nup153 (using Tpr as a scaffold), which is critical for early stages of NPC biogenesis. | Auxin-inducible degron (AID) depletion; NPC counting; kinase inhibitor experiments; phosphorylation assays; Co-IP | Genes & development | High | 30228202 |
| 2020 | Acute TPR depletion causes rapid transcriptomic changes closely related to those from loss of NXF1 or GANP (TREX-2 subunit), distinct from NUP153 or NUP50 depletion. TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) with NPCs, indicating TPR is an integral component of the TREX-2 mRNA export pathway. | Auxin-induced degron (AID) system for acute depletion; RNA-seq; NPC association assays for TREX-2 subunits | Nature communications | High | 32917881 |
| 2020 | TPR is required for efficient nuclear export of mRNAs and lncRNAs from short, intron-poor genes. In TPR-depleted cells, mRNAs from short transcripts accumulate in nuclear speckles while remaining bound to Nxf1, suggesting TPR acts downstream of Nxf1 recruitment to allow mRNAs to leave nuclear speckles and dock with the nuclear pore. | Nuclear/cytoplasmic RNA-seq in TPR-depleted cells; reporter constructs; co-localization with nuclear speckle markers; Nxf1 association assay | Nucleic acids research | Medium | 33091126 |
| 2021 | Tpr depletion generates transcription-dependent replication stress, DNA-RNA hybrids, DNA breaks, and genomic instability. Tpr interacts with RNA-processing proteins MATR3 and SUGP2, and with GANP (TREX-2 component). Tpr-deficient cells show slow and asymmetric replication forks, linking TPR to a network connecting replication forks with transcription, splicing, and mRNA export. | DNA fiber assays; electron microscopy of replication intermediates; proteomic interaction screen; siRNA depletion of interactors; immunoprecipitation | Nature communications | High | 34168151 |
| 2009 | Recombinant Tpr binds strongly and specifically to importin alpha, importin beta, and a CRM1-containing trimeric export complex via distinct binding sites. Nuclear import of Tpr is dependent on cytosolic factors and energy, efficiently mediated by the importin alpha/beta import pathway. Tpr preferentially binds CRM1 in an export complex, consistent with a role in protein export. | Solid-phase binding assays with recombinant proteins; in vitro nuclear import assays; competition binding experiments | BMC cell biology | Medium | 19835572 |
| 2012 | Tpr depletion impairs NES-dependent nuclear export of proteins and causes partial co-depletion of Nup153. Tpr depletion also affects levels and function of SUMO-protease SENP2, disrupting SUMOylation regulation at the nuclear pore. Tpr depletion triggers G0/G1 arrest and a p53-dependent senescent-like phenotype. | RNAi (siRNA) knockdown; NES-export assay; SUMO conjugation analysis; cell cycle analysis | PloS one | Medium | 21811608 |
| 2015 | Tpr interacts with Aurora A kinase via its central domain but not with Aurora B. Tpr depletion reduces Aurora A expression levels, centrosomal localization, and phosphorylation. Tpr also sequesters excess Aurora A at centrosomes to safeguard spindle bipolarity. Aurora A inhibitor Alisertib disrupts centrosomal localization of Tpr and induces mitotic catastrophe. | Co-immunoprecipitation; siRNA knockdown; overexpression; immunofluorescence; domain mapping | Cell cycle | Medium | 25789545 |
| 2019 | TPR associates with lamin B1 (but not lamin A/C). TPR depletion affects lamin B1 organization within the nuclear lamina (detected by STED microscopy) and alters NPC distribution within the nuclear envelope; this effect is reversed by simultaneous lamin A/C knockdown or lamin B1 overexpression. | Co-immunoprecipitation; STED microscopy; siRNA knockdown; double knockdown epistasis | Cellular and molecular life sciences | Medium | 30762072 |
| 1992 | The human tpr gene encodes a large protein (2094 amino acids, designated tpr-L) with extensive coiled-coil regions and a highly acidic C-terminal domain. The amino-terminal sequences are those that appear in oncogenic kinase fusions. | cDNA cloning and sequencing; structural prediction; tissue expression analysis | Oncogene | Medium | 1437155 |
| 1998 | Distinct molecular segments of Tpr confer different topogenetic properties: a short region in the C-terminal domain is essential and sufficient for nuclear import; the N-terminal coiled-coil domain, when imported into the nucleus, mediates association with the NPC via segments containing heptad repeat clusters. | Transfection of deletion mutants and chimeric Tpr-pyruvate kinase constructs in mammalian cells; immunofluorescence localization | Experimental cell research | Medium | 9828100 |
| 1988 | The TPR-MET oncogene encodes p65tpr-met, a constitutively active protein-tyrosine kinase that is autophosphorylated in vitro on tyrosine residues. In vivo, p65tpr-met is phosphorylated on both serine and tyrosine residues. | Immunocomplex kinase assay; in vitro autophosphorylation; in vivo 32P labeling; cell-surface iodination | Proceedings of the National Academy of Sciences | High | 3277171 |
| 1995 | A single tyrosine residue (Tyr489) in the C-terminus of Tpr-Met is essential for efficient cell transformation. Tyr489 is required for association with Grb2, phosphatidylinositol 3-kinase, phospholipase Cγ, and SHPTP2/Syp. Transformation of fibroblasts depends on downstream pathways of Shc and Grb2, while PI3K, PLCγ, and SHPTP2 pathways alone are insufficient. | Site-directed mutagenesis (Tyr→Phe); transformation assays in Fr3T3 fibroblasts; co-immunoprecipitation of signaling proteins | Oncogene / The Journal of biological chemistry | High | 7838524 8662733 |
| 1999 | Loss of the juxtamembrane domain of Met is essential for Tpr-Met oncogenic transformation. Tpr-juxtaMet (containing juxtamembrane domain aa 962-1009) strongly inhibits transformation, proliferation, anchorage-independent growth, motility, and invasion without altering kinase activity. The juxtamembrane domain impairs association of Tpr-Met with cytoplasmic signal transducers and downstream signaling. | Chimeric protein construction; cell transformation assays; in vitro kinase assay; co-immunoprecipitation | Oncogene | High | 10435641 |
| 2007 | Tpr-Met oncogenic activation is dependent on cytoplasmic localization and exclusion from the endocytic/lysosomal degradation pathway. Plasma membrane targeting of Tpr-Met allows Cbl-dependent ubiquitination and degradation, reducing transforming activity. Cytoplasmic Tpr-Met lacks the Cbl-binding site and escapes downregulation; ubiquitination of cytosolic Tpr-Met alone does not alter its transforming activity. | Membrane-targeting constructs; Cbl co-expression; ubiquitination assays; transformation assays; protein stability measurements | Oncogene | Medium | 17533376 |
| 2012 | Tpr depletion caused reduction in nuclear pore number and reduction in inner nuclear filaments (by electron microscopy). Tpr depletion increased p53 nuclear accumulation and facilitated autophagy. Tpr controls HSP70 and HSF1 mRNA export, and p53 trafficking via CRM1/exportin. | siRNA knockdown; electron microscopy; immunofluorescence; mRNA export assays; Western blotting | Scientific reports | Medium | 23170199 |
| 1996 | Tpr is a phosphoprotein of the nuclear pore complex; immunoprecipitation from 32P-labeled cells confirms in vivo phosphorylation. The protein has multiple leucine zipper motifs and numerous predicted phosphorylation sites. | Immunoprecipitation from 32P-orthophosphate-labeled cells; monoclonal antibody characterization; cDNA library screening; immunofluorescence | Journal of cellular biochemistry | Medium | 8726355 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2003 | TPR proteins: the versatile helix. | Trends in biochemical sciences | 914 | 14659697 |
| 1998 | The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. | The EMBO journal | 682 | 9482716 |
| 1991 | The TPR snap helix: a novel protein repeat motif from mitosis to transcription. | Trends in biochemical sciences | 413 | 1882418 |
| 1999 | Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. | The EMBO journal | 358 | 9927435 |
| 1988 | Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. | Proceedings of the National Academy of Sciences of the United States of America | 210 | 3277171 |
| 1997 | Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. | The Journal of cell biology | 199 | 9024684 |
| 2010 | Versatile TPR domains accommodate different modes of target protein recognition and function. | Cell stress & chaperones | 194 | 21153002 |
| 2004 | Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. | The EMBO journal | 181 | 15577939 |
| 1991 | The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. | Proceedings of the National Academy of Sciences of the United States of America | 181 | 2052572 |
| 2007 | TPRpred: a tool for prediction of TPR-, PPR- and SEL1-like repeats from protein sequences. | BMC bioinformatics | 177 | 17199898 |
| 2003 | TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. | Current biology : CB | 172 | 12956947 |
| 1998 | Major binding sites for the nuclear import receptor are the internal nucleoporin Nup153 and the adjacent nuclear filament protein Tpr. | The Journal of cell biology | 166 | 9531546 |
| 2018 | Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance. | Proceedings of the National Academy of Sciences of the United States of America | 162 | 29432165 |
| 2005 | Differential control of glucocorticoid receptor hormone-binding function by tetratricopeptide repeat (TPR) proteins and the immunosuppressive ligand FK506. | Biochemistry | 155 | 15697228 |
| 2003 | Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy. | American journal of human genetics | 154 | 14574644 |
| 2002 | Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export. | The Journal of cell biology | 151 | 11839768 |
| 2011 | IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. | Journal of immunology (Baltimore, Md. : 1950) | 146 | 21813773 |
| 2007 | From Tpr-Met to Met, tumorigenesis and tubes. | Oncogene | 144 | 17322912 |
| 2008 | Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint. | Genes & development | 129 | 18981471 |
| 2005 | Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein. | Molecular cell | 114 | 15664193 |
| 1996 | Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein. | The Journal of biological chemistry | 110 | 8662733 |
| 2003 | Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system. | The EMBO journal | 107 | 12853476 |
| 1994 | Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex. | The Journal of cell biology | 104 | 7798308 |
| 2020 | Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway. | Nature communications | 100 | 32917881 |
| 2003 | TPR-mediated interaction of RapC with ComA inhibits response regulator-DNA binding for competence development in Bacillus subtilis. | Molecular microbiology | 100 | 12950917 |
| 1997 | A Drosophila Tpr protein homolog is localized both in the extrachromosomal channel network and to nuclear pore complexes. | Journal of cell science | 100 | 9152019 |
| 2015 | OsBRI1 Activates BR Signaling by Preventing Binding between the TPR and Kinase Domains of OsBSK3 via Phosphorylation. | Plant physiology | 93 | 26697897 |
| 1998 | Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export. | The Journal of cell biology | 93 | 9864356 |
| 2007 | Structure and stability of designed TPR protein superhelices: unusual crystal packing and implications for natural TPR proteins. | Acta crystallographica. Section D, Biological crystallography | 91 | 17582171 |
| 1996 | Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. | The Journal of clinical investigation | 91 | 8675700 |
| 2010 | Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore. | Nucleus (Austin, Tex.) | 86 | 21113270 |
| 1992 | Cloning, expression, and sequencing of a protease gene (tpr) from Porphyromonas gingivalis W83 in Escherichia coli. | Infection and immunity | 85 | 1322368 |
| 2010 | AlgK is a TPR-containing protein and the periplasmic component of a novel exopolysaccharide secretin. | Structure (London, England : 1993) | 81 | 20159471 |
| 2013 | Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. | PLoS neglected tropical diseases | 80 | 23696912 |
| 2010 | Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. | The Journal of biological chemistry | 80 | 20133940 |
| 2001 | The nucleoporin Nup98 associates with the intranuclear filamentous protein network of TPR. | Proceedings of the National Academy of Sciences of the United States of America | 79 | 11248057 |
| 1998 | Identification of a novel cellular TPR-containing protein, SGT, that interacts with the nonstructural protein NS1 of parvovirus H-1. | Journal of virology | 75 | 9557704 |
| 2014 | A novel fusion of TPR and ALK in lung adenocarcinoma. | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | 73 | 24736082 |
| 2011 | Self-recognition mechanism of MamA, a magnetosome-associated TPR-containing protein, promotes complex assembly. | Proceedings of the National Academy of Sciences of the United States of America | 70 | 21784982 |
| 1995 | Efficient cell transformation by the Tpr-Met oncoprotein is dependent upon tyrosine 489 in the carboxy-terminus. | Oncogene | 70 | 7838524 |
| 2011 | The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. | RNA (New York, N.Y.) | 69 | 21613532 |
| 1997 | Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes. | Genes, chromosomes & cancer | 68 | 9172002 |
| 2012 | Structure of the TPR domain of AIP: lack of client protein interaction with the C-terminal α-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition. | PloS one | 64 | 23300914 |
| 1999 | Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET. | Oncogene | 62 | 10435641 |
| 2008 | Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. | Molecular and cellular biology | 61 | 18794356 |
| 2013 | Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis. | The Journal of cell biology | 58 | 24344181 |
| 2012 | Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA. | PloS one | 57 | 22253824 |
| 2004 | Multiple TPR motifs characterize the Fanconi anemia FANCG protein. | DNA repair | 57 | 14697762 |
| 1995 | Fission yeast TPR-family protein nuc2 is required for G1-arrest upon nitrogen starvation and is an inhibitor of septum formation. | Journal of cell science | 56 | 7622618 |
| 1987 | Characterization of the rearranged tpr-met oncogene breakpoint. | Molecular and cellular biology | 55 | 3821733 |
| 2011 | Macrocycles that inhibit the binding between heat shock protein 90 and TPR-containing proteins. | ACS chemical biology | 53 | 21950602 |
| 2011 | Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle orientation. | The Journal of cell biology | 53 | 22024168 |
| 1993 | BIMA, a TPR-containing protein required for mitosis, localizes to the spindle pole body in Aspergillus nidulans. | The Journal of cell biology | 51 | 8432735 |
| 2011 | Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent. | Journal of translational medicine | 50 | 21235734 |
| 1997 | Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr-Met involves GRB2. | Oncogene | 49 | 9038378 |
| 1990 | Mouse vimentin: structural relationship to fos, jun, CREB and tpr. | Oncogene | 48 | 2140597 |
| 2002 | Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted Tpr-less nuclei in living mammalian cells. | Genes to cells : devoted to molecular & cellular mechanisms | 47 | 11952838 |
| 2020 | TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes. | Nucleic acids research | 46 | 33091126 |
| 2012 | Regulation of autophagy by nucleoporin Tpr. | Scientific reports | 46 | 23170199 |
| 2000 | An aspartic acid residue in TPR-1, a specific region of protein-priming DNA polymerases, is required for the functional interaction with primer terminal protein. | Journal of molecular biology | 46 | 11090274 |
| 2015 | Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways. | PloS one | 44 | 26244501 |
| 2008 | Chaperone ligand-discrimination by the TPR-domain protein Tah1. | The Biochemical journal | 44 | 18412542 |
| 2019 | Architecture of the Cellulose Synthase Outer Membrane Channel and Its Association with the Periplasmic TPR Domain. | Structure (London, England : 1993) | 43 | 31604608 |
| 1997 | The prp1+ gene required for pre-mRNA splicing in Schizosaccharomyces pombe encodes a protein that contains TPR motifs and is similar to Prp6p of budding yeast. | Genetics | 43 | 9286671 |
| 2010 | Self-association of TPR domains: Lessons learned from a designed, consensus-based TPR oligomer. | Proteins | 41 | 20455268 |
| 2018 | Tpr regulates the total number of nuclear pore complexes per cell nucleus. | Genes & development | 40 | 30228202 |
| 2005 | Proximity of TPR and NTRK1 rearranging loci in human thyrocytes. | Cancer research | 40 | 15805251 |
| 1992 | The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain. | Oncogene | 40 | 1437155 |
| 2007 | Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway. | Oncogene | 39 | 17533376 |
| 2020 | Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma. | Autophagy | 36 | 32207633 |
| 2010 | The repeat domain of the type III effector protein PthA shows a TPR-like structure and undergoes conformational changes upon DNA interaction. | Proteins | 36 | 20848643 |
| 2006 | TPR Proteins in Plant Hormone Signaling. | Plant signaling & behavior | 36 | 19704665 |
| 2021 | The human nucleoporin Tpr protects cells from RNA-mediated replication stress. | Nature communications | 35 | 34168151 |
| 2013 | Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient. | BMC microbiology | 34 | 23898829 |
| 1990 | TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines. | Proceedings of the National Academy of Sciences of the United States of America | 34 | 2300559 |
| 2013 | Chaperone-interacting TPR proteins in Caenorhabditis elegans. | Journal of molecular biology | 33 | 23727266 |
| 2004 | RoXaN, a novel cellular protein containing TPR, LD, and zinc finger motifs, forms a ternary complex with eukaryotic initiation factor 4G and rotavirus NSP3. | Journal of virology | 33 | 15047801 |
| 1998 | Molecular segments of protein Tpr that confer nuclear targeting and association with the nuclear pore complex. | Experimental cell research | 33 | 9828100 |
| 1993 | Characterization of the tpr gene product and isolation of a specific protease-deficient mutant of Porphyromonas gingivalis W83. | Infection and immunity | 33 | 8406803 |
| 2004 | The crystal structure of Helicobacter cysteine-rich protein C at 2.0 A resolution: similar peptide-binding sites in TPR and SEL1-like repeat proteins. | Journal of molecular biology | 32 | 15223324 |
| 2015 | The Non-canonical Tetratricopeptide Repeat (TPR) Domain of Fluorescent (FLU) Mediates Complex Formation with Glutamyl-tRNA Reductase. | The Journal of biological chemistry | 31 | 26037924 |
| 2011 | Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells. | PloS one | 31 | 21811608 |
| 2009 | Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr. | BMC cell biology | 30 | 19835572 |
| 2005 | RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis. | Cancer gene therapy | 30 | 15719029 |
| 2004 | The human small glutamine-rich TPR-containing protein is required for progress through cell division. | Experimental cell research | 30 | 14729056 |
| 2001 | Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma. | The Journal of pathology | 29 | 11523050 |
| 2014 | Roles of the nucleoporin Tpr in cancer and aging. | Advances in experimental medicine and biology | 28 | 24563354 |
| 2014 | Phosphorylation of nucleoporin Tpr governs its differential localization and is required for its mitotic function. | Journal of cell science | 28 | 24938596 |
| 2015 | Therapeutic potential of mitotic interaction between the nucleoporin Tpr and aurora kinase A. | Cell cycle (Georgetown, Tex.) | 27 | 25789545 |
| 2008 | The human TPR protein TTC4 is a putative Hsp90 co-chaperone which interacts with CDC6 and shows alterations in transformed cells. | PloS one | 27 | 18320024 |
| 2007 | TPR-Mediated self-association of plant SGT1. | Biochemistry | 27 | 17877371 |
| 2007 | Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster. | Journal of cell science | 27 | 17878237 |
| 2020 | Cancer-derived UTX TPR mutations G137V and D336G impair interaction with MLL3/4 complexes and affect UTX subcellular localization. | Oncogene | 26 | 32071397 |
| 2019 | TPR-containing proteins control protein organization and homeostasis for the endoplasmic reticulum. | Critical reviews in biochemistry and molecular biology | 26 | 31023093 |
| 2002 | Structures and dynamics of Drosophila Tpr inconsistent with a static, filamentous structure. | Experimental cell research | 26 | 12027452 |
| 2021 | Truncation of the TPR domain of OGT alters substrate and glycosite selection. | Analytical and bioanalytical chemistry | 25 | 34725712 |
| 2019 | Nuclear pore protein TPR associates with lamin B1 and affects nuclear lamina organization and nuclear pore distribution. | Cellular and molecular life sciences : CMLS | 25 | 30762072 |
| 2012 | The TPR domain in the host Cyp40-like cyclophilin binds to the viral replication protein and inhibits the assembly of the tombusviral replicase. | PLoS pathogens | 25 | 22346747 |
| 2004 | Novel interaction partners of the TPR/MET tyrosine kinase. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 24 | 15546961 |
| 1996 | Product of the oncogene-activating gene Tpr is a phosphorylated protein of the nuclear pore complex. | Journal of cellular biochemistry | 24 | 8726355 |
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