Affinage

TPR

Nucleoprotein TPR · UniProt P12270

Length
2363 aa
Mass
267.3 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPR is a large coiled-coil nucleoporin that forms the intranuclear basket filaments of the nuclear pore complex, where it serves as a multifunctional scaffold integrating mRNA export, nuclear retention of unspliced transcripts, spindle assembly checkpoint signaling, and NPC biogenesis control (PMID:9024684, PMID:30228202, PMID:18981471). TPR anchors the TREX-2 complex (GANP/PCID2/ENY2) at the NPC and is specifically required for nuclear export of mRNAs from intron-poor genes via the Nxf1 pathway, acting downstream of Nxf1 to release transcripts from nuclear speckles, while simultaneously retaining unspliced intron-containing mRNAs in the nucleus (PMID:32917881, PMID:33091126, PMID:21613532). During interphase, TPR stabilizes Mad1 and Mad2 protein levels and recruits the Mad1–Mad2 complex to NPCs, with CDK1-mediated phosphorylation at S2059 governing the TPR–Mad1 interaction and ensuring spindle assembly checkpoint robustness; TPR also cooperates with dynein/dynactin to promote proper chromosome segregation (PMID:24344181, PMID:24938596, PMID:20133940). TPR negatively regulates NPC number by scaffolding ERK-mediated phosphorylation of Nup153, and its N-terminal coiled-coil domain provides the dimerization/activation module in oncogenic fusions such as TPR-MET (PMID:30228202, PMID:3821733, PMID:3277171).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1987 High

    The discovery of the TPR-MET chromosomal rearrangement established that TPR sequences provide an N-terminal dimerization module fused to the MET kinase domain, founding the concept of TPR as an oncogene contributor.

    Evidence Nucleotide sequencing of rearranged and unrearranged tpr/met genomic fragments

    PMID:3821733

    Open questions at the time
    • Normal TPR function was unknown
    • Whether TPR coiled-coil domain was sufficient for dimerization was not directly tested
  2. 1988 High

    Demonstration that TPR-MET encodes a constitutively active tyrosine kinase (p65) established that the TPR moiety drives ligand-independent kinase activation through enforced dimerization.

    Evidence Immunocomplex kinase assay and phosphoamino acid analysis of p65(tpr-met)

    PMID:3277171

    Open questions at the time
    • Structural basis of TPR-mediated dimerization unresolved
    • Contribution of individual TPR heptad repeats to activation unknown
  3. 1995 High

    Identification of Tyr489 as the essential signaling residue in TPR-MET defined the downstream effector requirements (Grb2, PI3K, Shc) for transformation, dissecting how the fusion signals.

    Evidence Tyr-to-Phe mutagenesis with transformation assays and co-IP of signaling partners

    PMID:7838524 PMID:8662733

    Open questions at the time
    • Role of TPR-derived sequences beyond dimerization in signaling not addressed
    • In vivo tumor models not tested
  4. 1997 High

    Correcting earlier reports, immunoelectron microscopy with multiple antibodies demonstrated that TPR exclusively localizes to the intranuclear (basket) filaments of the NPC, not the cytoplasmic face, redefining its functional context.

    Evidence Immunoelectron microscopy with antibodies to multiple distinct TPR epitopes across mammalian and amphibian cells

    PMID:9024684

    Open questions at the time
    • How TPR assembles into basket filaments was unknown
    • Whether TPR is essential for basket structure was untested
  5. 1998 High

    Domain mapping revealed that the N-terminal coiled-coil mediates NPC association while the C-terminus contains the NLS; overexpression causing poly(A)+ RNA nuclear accumulation provided the first link between TPR and mRNA export.

    Evidence Expression of full-length and deletion mutants in mammalian cells with poly(A)+ RNA FISH

    PMID:9828100 PMID:9864356

    Open questions at the time
    • Whether TPR directly contacts RNA or acts via protein partners was unknown
    • Export pathway specificity not determined
  6. 2001 High

    Discovery of direct TPR–Nup98 binding and their colocalization in intranuclear filaments suggested that TPR participates in an intranuclear transport network extending beyond the NPC basket.

    Evidence In vitro binding of translated proteins combined with double-immunoEM

    PMID:11248057

    Open questions at the time
    • Functional consequence of TPR–Nup98 interaction on transport not tested
    • Whether other nucleoporins participate in intranuclear filaments unknown
  7. 2002 High

    Anti-TPR antibody injection experiments established that TPR is specifically required for leucine-rich NES-dependent nuclear protein export, while NLS-mediated import is unaffected, distinguishing TPR's directionality in transport.

    Evidence Antibody microinjection into interphase and mitotic cells with import/export reporter assays

    PMID:11839768 PMID:11952838

    Open questions at the time
    • Whether TPR acts as a direct export factor or scaffold was unresolved
    • Pathway specificity (CRM1 vs Nxf1) not yet discriminated
  8. 2008 High

    Identification of direct TPR–Mad1–Mad2 binding and the requirement of TPR for interphase NPC localization of checkpoint proteins established an unexpected role for the nuclear basket in spindle assembly checkpoint priming.

    Evidence Mass spectrometry of Mad2-associated factors, direct binding assays, siRNA knockdown with checkpoint readouts in HeLa cells

    PMID:18981471

    Open questions at the time
    • Whether TPR stabilizes Mad1/Mad2 protein levels or only localizes them was unclear
    • Phosphoregulation of the interaction was unknown
  9. 2010 High

    Discovery of TPR interaction with dynein/dynactin and the lagging chromosome phenotype upon TPR depletion extended its mitotic roles beyond SAC signaling to direct involvement in chromosome segregation mechanics.

    Evidence Reciprocal co-IP, RNAi knockdown with rescue and dominant-negative experiments

    PMID:20133940

    Open questions at the time
    • Structural basis of TPR–dynein interaction not defined
    • Whether dynein interaction is direct or mediated by Mad1/Mad2 not fully resolved
  10. 2011 High

    Pathway-specific reporter assays revealed that TPR selectively retains unspliced mRNAs that use the Nxf1/CTE export route, while CRM1/Rev-dependent export is unaffected, establishing TPR as a quality-control checkpoint for intron-containing RNA at the NPC.

    Evidence RNAi knockdown with CTE vs RRE reporter mRNA export assays

    PMID:21613532

    Open questions at the time
    • Whether TPR directly recognizes intron-containing features or acts via cofactors was unknown
    • Relationship to TREX-2 not yet established
  11. 2013 High

    Demonstration that TPR stabilizes Mad1 and Mad2 protein levels (not just localization) during interphase via TM2 complex formation resolved how TPR contributes to SAC proteostasis independently of kinetochores and mRNA.

    Evidence Co-IP, protein half-life measurements, GFP-Mad2 rescue in TPR-depleted cells

    PMID:24344181

    Open questions at the time
    • Role of SUMO-isopeptidases SENP1/SENP2 in this stabilization not fully validated
    • Whether TPR-mediated stabilization involves ubiquitin-proteasome pathway unknown
  12. 2013 High

    Identification of KPNA2 as the importin alpha mediating TPR nuclear import, with nanomolar NLS-binding affinity, and discovery that progerin-induced Ran gradient disruption impairs TPR import linked NPC basket assembly to laminopathy pathology.

    Evidence NLS-swap experiments, binding affinity measurements, analysis in HGPS patient fibroblasts

    PMID:23649804

    Open questions at the time
    • Whether reduced TPR import contributes to specific HGPS phenotypes not tested functionally
    • Whether other import receptors can substitute for KPNA2 unknown
  13. 2014 High

    Identification of CDK1-mediated S2059 phosphorylation as the switch governing TPR–Mad1 interaction provided the first phosphoregulatory mechanism linking cell cycle kinase activity to NPC-based SAC signaling.

    Evidence MS-based phosphosite identification, in vitro kinase assay, phosphomutant rescue in siRNA-depleted cells

    PMID:24938596

    Open questions at the time
    • Whether S2059 phosphorylation is the sole regulatory switch or acts with additional modifications unknown
    • Structural consequences of phosphorylation on TPR–Mad1 interface not resolved
  14. 2018 High

    Acute TPR depletion causing increased NPC number revealed that TPR negatively regulates NPC biogenesis by scaffolding ERK-mediated phosphorylation of Nup153, establishing a signaling-based feedback on pore density.

    Evidence AID-mediated acute depletion, NPC counting, ERK inhibition epistasis, co-IP

    PMID:30228202

    Open questions at the time
    • Which Nup153 phosphosites are ERK targets on the TPR scaffold not mapped
    • Whether NPC number control feeds back on gene expression was not addressed
  15. 2020 High

    Transcriptomic comparison of acute TPR, NXF1, and GANP depletions revealed overlapping gene expression changes, and co-IP showed TPR anchors the TREX-2 complex at NPCs, integrating TPR into the TREX-2 mRNA export pathway.

    Evidence Auxin-inducible degron system with RNA-seq and co-IP of TREX-2 subunits

    PMID:32917881

    Open questions at the time
    • Direct versus indirect interaction between TPR and GANP not structurally resolved
    • Whether all TREX-2 functions require NPC-anchored TPR unknown
  16. 2020 High

    Fractionated RNA-seq after TPR depletion identified intron-poor and short genes as the specifically affected class, with their mRNAs accumulating in nuclear speckles while still bound to Nxf1, placing TPR's export function downstream of Nxf1 loading.

    Evidence Nuclear/cytoplasmic RNA fractionation-seq, reporter constructs, immunofluorescence in TPR-depleted cells

    PMID:33091126

    Open questions at the time
    • Mechanism by which TPR releases Nxf1-loaded mRNPs from speckles unknown
    • Whether speckle retention is a cause or consequence of export failure not determined
  17. 2021 High

    Discovery that TPR depletion generates transcription-dependent replication stress, DNA breaks, and R-loops, with proteomic identification of MATR3 and SUGP2 as interactors, revealed TPR's role in coordinating transcription with replication to maintain genome stability.

    Evidence DNA fiber assays, EM of replication intermediates, R-loop detection, complementary proteomics, co-IP

    PMID:34168151

    Open questions at the time
    • Whether genome instability is a direct consequence of export failure or an independent TPR function unclear
    • MATR3 and SUGP2 interaction directionality and stoichiometry not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TPR basket filament assembly, how TPR discriminates intron-poor mRNPs for export, whether its mRNA export and SAC functions are mechanistically coupled, and how TPR's multiple scaffolding roles are coordinated during the cell cycle.
  • No high-resolution structure of TPR or TPR–Mad1 complex
  • Mechanism of intron-poor mRNA selectivity at the molecular level unknown
  • Whether mRNA export and checkpoint functions share regulatory inputs untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 4 GO:0005635 nuclear envelope 3
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-1640170 Cell Cycle 5 R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
DYNLL1KPNA2MAD1L1MAD2L1MATR3MCM3APNUP153NUP98
Complex memberships
Nuclear pore complex (NPC basket)TPR-Mad1-Mad2 (TM2) complexTREX-2 mRNA export complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Tpr (translocated promoter region) is a large coiled-coil protein (~265 kDa) localized to the cytoplasmic surface of the nuclear pore complex (NPC) in rat liver, identified by monoclonal antibody RL30; its amino-terminal ~150-250 amino acids appear in oncogenic fusions with Met, Trk, and Raf kinase domains. Immunogold electron microscopy, immunofluorescence, peptide sequencing, in vitro translation The Journal of cell biology High 7798308
1997 Human protein p270/Tpr is exclusively localized to the intranuclear filaments attached to the nucleoplasmic annulus of the NPC (not the cytoplasmic surface), forming filament bundles extending up to 350 nm into the nuclear interior; this was demonstrated with multiple antibodies against different Tpr epitopes across mammalian and amphibian cells. Immunoelectron microscopy with multiple antibodies to distinct Tpr epitopes, cDNA cloning, immunobiochemistry The Journal of cell biology High 9024684
1998 Tpr's NH2-terminal coiled-coil domain mediates association with the nucleoplasmic face of the NPC, while an acidic COOH-terminal domain contains a nuclear localization sequence; ectopic expression of full-length Tpr or NPC-associating domains causes dramatic nuclear accumulation of poly(A)+ RNA, implicating Tpr in mRNA export. Expression of full-length and deletion mutant Tpr in mammalian cells, immunofluorescence, poly(A)+ RNA in situ hybridization The Journal of cell biology High 9864356
2001 TPR directly binds Nup98 in vitro, and via Nup98 also associates with Nup96; TPR and Nup98 colocalize in a filamentous intranuclear network extending from NPCs to perinucleolar regions, suggesting an intranuclear phase of transport involving these nucleoporins. In vitro binding of translated proteins, double-immunofluorescence microscopy, overexpression of myc-tagged fusion proteins, double-immunoelectron microscopy Proceedings of the National Academy of Sciences of the United States of America High 11248057
2002 Tpr is concentrated within the nuclear basket of the NPC (similar to Nup153 and Nup98); injection of anti-Tpr antibodies into mitotic or interphase cells inhibits leucine-rich NES-dependent nuclear protein export without affecting basic NLS-mediated nuclear import, establishing Tpr's role in nuclear protein export. Light and EM immunolocalization, GFP-Tpr live-cell imaging, antibody microinjection into mitotic and interphase cells, nuclear import/export assays The Journal of cell biology High 11839768
2002 Antibody-mediated depletion of Tpr from nuclei causes poly(A)+ RNA to accumulate in SC35-positive nuclear speckle clusters (larger and fewer in number), without affecting SV40 T-NLS import or Rev NES-dependent export, indicating Tpr is specifically required for intranuclear dynamics and processing/transport of RNA Pol II transcripts. Cytoplasmic microinjection of anti-Tpr antibodies to reconstitute Tpr-less nuclei, immunofluorescence, poly(A)+ RNA FISH Genes to cells High 11952838
2008 Tpr directly binds Mad1 and Mad2; Tpr depletion in HeLa cells disrupts NPC localization of Mad1 and Mad2 during interphase, reduces Mad1-bound Mad2 levels, and decreases Mad1 at kinetochores during prometaphase, impairing APC(Cdc20) inhibition and the spindle assembly checkpoint. Mass spectrometry of affinity-purified Mad2-associated factors, direct binding assays, siRNA knockdown, immunofluorescence Genes & development High 18981471
2009 Tpr binds strongly and specifically to importin alpha, importin beta, and CRM1-containing trimeric export complexes via distinct sites; nuclear import of Tpr is dependent on cytosolic factors and energy and is efficiently mediated by the importin alpha/beta pathway. Solid-phase binding assays with recombinant proteins, in vitro nuclear import assay BMC cell biology High 19835572
2010 Tpr associates with dynein and dynactin motor complexes; Tpr knockdown causes lagging chromosome phenotype and disrupts spindle checkpoint proteins (Mad1/Mad2) expression and localization; overexpression of Tpr enhances multinucleated cell formation; rescue and dominant-negative experiments confirm Tpr promotes proper chromosome segregation through interaction with dynein light chain. Co-immunoprecipitation, RNAi knockdown, rescue experiments, immunofluorescence, dominant-negative overexpression The Journal of biological chemistry High 20133940
2011 Tpr regulates export of mRNAs with retained introns that traffic through the Nxf1/Nxt1 (CTE) pathway but not the Crm1/Rev pathway; even modest Tpr knockdown significantly increases export and translation from CTE-containing mRNA with retained introns, without affecting completely spliced mRNA. RNAi knockdown, reporter mRNA export assays (CTE vs RRE reporters), Western blotting RNA High 21613532
2012 Tpr knockdown in mammalian cells dramatically enhances export of CTE-containing unspliced RNA; this regulation requires Tpr's localization to the NPC (NPC-unanchored Tpr cannot perform this function) and is independent of Sam68 and Tap/Nxf1; Nup153 (required for NPC anchoring of Tpr) similarly regulates unspliced RNA export. siRNA knockdown, reporter export assays, rescue with siRNA-resistant Tpr, immunofluorescence PloS one High 22253824
2013 Tpr stabilizes Mad1 and Mad2 protein levels before mitosis by forming a TM2 (Tpr/Mad1/Mad2) complex at NPCs during interphase; Tpr is required for Mad1–c-Mad2 recruitment to NPCs; Tpr stabilizes Mad1 and Mad2 in an mRNA- and kinetochore-independent manner; Tpr may regulate SAC proteostasis through SUMO-isopeptidases SENP1/SENP2 at NPCs. Co-immunoprecipitation, siRNA depletion, protein half-life measurements, GFP-Mad2 overexpression rescue, immunofluorescence The Journal of cell biology High 24344181
2013 Tpr is imported into the nucleus via KPNA2 (importin alpha), which binds the bipartite NLS in Tpr with nanomolar affinity; Progerin (mutant lamin A in Hutchinson-Gilford Progeria) disrupts the nuclear/cytoplasmic Ran distribution, causing defective Tpr nuclear import because large cargo transport is particularly sensitive to changes in Ran gradient. NLS swapping experiments, binding affinity measurements, cell fractionation, fluorescence microscopy in HGPS fibroblasts The Journal of cell biology High 23649804
2014 Tpr is phosphorylated at S2059 by CDK1 and at S2094 by protein kinase A; CDK1-mediated S2059 phosphorylation is required for Tpr interaction with Mad1 and for proper localization of Mad1 and Mad2; abrogation of S2059 phosphorylation causes cell cycle defects; phosphorylated S2059-Tpr distinctly localizes with chromatin during telophase. Mass spectrometry-based phosphosite identification, kinase assays, phospho-specific antibodies, siRNA rescue with phosphomutants, immunofluorescence Journal of cell science High 24938596
2018 Depletion of Tpr (but not Nup153) dramatically increases the total number of NPCs per nucleus; this negative regulation occurs via ERK (MAPK) pathway phosphorylation, where Tpr serves as a scaffold for ERK to phosphorylate Nup153, which is critical for early stages of NPC biogenesis. AID-mediated acute depletion, NPC counting, kinase inhibition, epistasis experiments, co-immunoprecipitation Genes & development High 30228202
2020 Acute TPR depletion using an Auxin-Induced Degron system causes rapid transcriptomic changes similar to NXF1 or GANP (TREX-2 complex) depletion; TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) with NPCs, resulting in abnormal RNA transcription and export, establishing TPR as an integral component of the TREX-2 mRNA export pathway. Auxin-Induced Degron system, RNA-seq transcriptomics, co-immunoprecipitation, comparison of nucleoporin depletions Nature communications High 32917881
2020 TPR is specifically required for efficient nuclear export of mRNAs and lncRNAs from short, intron-poor genes; in TPR-depleted cells these mRNAs 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. Fractionated RNA-seq of nucleus vs. cytosol in TPR-depleted cells, reporter constructs, immunofluorescence Nucleic acids research High 33091126
2021 Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability; Tpr-deficient cells show slow/asymmetric replication forks and elevated DNA-RNA hybrids; proteomic approaches identify Tpr-interacting proteins MATR3 and SUGP2 (RNA processing); Tpr interacts with GANP (TREX-2 complex), physically connecting replication forks with transcription, splicing, and mRNA export machinery. DNA fiber assays, electron microscopy of replication intermediates, complementary proteomics, Co-immunoprecipitation, siRNA knockdown, R-loop detection Nature communications High 34168151
2015 Tpr interacts with Aurora A kinase via its central coiled-coil domain; Tpr depletion reduces Aurora A expression levels, centrosomal localization, and phosphorylation; Tpr and Aurora A mutually regulate each other and Tpr sequesters extra Aurora A to safeguard spindle bipolarity. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, Aurora A inhibitor (Alisertib) treatment Cell cycle Medium 25789545
2011 In Tpr-depleted cells, silencing of Tpr triggers G0-G1 arrest and senescent-like phenotype dependent on p53; Tpr depletion impairs NES-dependent nuclear export of proteins; Tpr depletion affects SUMO-protease SENP2 levels/function, altering SUMOylation at the nuclear pore. RNAi knockdown, cell cycle analysis, immunofluorescence, Western blotting PloS one Medium 21811608
2012 Tpr depletion reduces nuclear pore numbers and intranuclear filament number; Tpr-depleted cells show increased p53 nuclear accumulation and autophagy; Tpr controls HSP70 and HSF1 mRNA export and p53 trafficking with karyopherin CRM1. siRNA knockdown, electron microscopy, immunofluorescence, Western blotting Scientific reports Medium 23170199
1998 Molecular segments of Tpr were identified: a short C-terminal region is necessary and sufficient for nuclear import of Tpr and can confer nuclear accumulation on pyruvate kinase; the N-terminal coiled-coil domain contains clusters of heptad repeats that mediate NPC association when present in the nucleus. Expression of Tpr deletion mutants and chimeric proteins in mammalian cells, immunofluorescence Experimental cell research Medium 9828100
1987 The TPR-MET oncogene was generated by chromosomal rearrangement (recombination event) fusing sequences from the tpr locus on chromosome 1 (following an Alu repetitive sequence) to the met locus on chromosome 7; the rearrangement places tpr-encoded sequences upstream of the MET kinase domain. Nucleotide sequencing of rearranged genomic locus and unrearranged tpr/met fragments Molecular and cellular biology High 3821733
1988 The TPR-MET oncogene encodes p65(tpr-met), a constitutively active protein-tyrosine kinase that autophosphorylates on tyrosine in vitro; in vivo p65(tpr-met) is phosphorylated on serine and tyrosine, while p140(met) is phosphorylated on serine and threonine. Immunocomplex kinase assay, in vitro autophosphorylation, cell-surface iodination, phosphoamino acid analysis Proceedings of the National Academy of Sciences of the United States of America High 3277171
1995 A single tyrosine residue (Tyr489) in the C-terminus of Tpr-Met is essential for efficient transformation of fibroblasts; Y489 is required for association with Grb2, phosphatidylinositol 3-kinase activation, and phospholipase Cgamma/SHPTP2 association in vivo; mutation of Y489 does not affect exogenous kinase activity toward casein. Tyrosine-to-phenylalanine mutagenesis, transformation assays, co-immunoprecipitation, kinase assays Oncogene High 7838524
1996 Cell transformation by Tpr-Met requires signaling pathways downstream of Shc and Grb2; pathways downstream of PI3-kinase, PLCgamma, and SHPTP2/Syp alone are insufficient for transformation; a Tpr-Met mutant selectively unable to associate with Grb2 was generated to dissect these pathways. Generation of Tpr-Met mutants selectively defective in adaptor binding, transformation assays, co-immunoprecipitation The Journal of biological chemistry High 8662733
1999 Loss of the juxtamembrane domain of MET (which occurs in the TPR-MET rearrangement) is essential for oncogenic activation; a chimeric Tpr-juxtaMet retaining the juxtamembrane domain (aa 962-1009) strongly inhibits transformation and downstream signaling/adaptor recruitment despite equivalent kinase activity. Construction of chimeric Tpr-juxtaMet, transformation assays (proliferation, soft agar, motility, invasion), co-immunoprecipitation of signaling molecules Oncogene High 10435641
1992 The human TPR gene encodes a 726 amino acid protein with extensive alpha-helical regions and three heptad repeat motifs characteristic of coiled-coil conformation; alternative splicing can extend the C-terminal domain; its N-terminal sequences contribute to oncogenic fusions with MET, RAF kinase domains. cDNA cloning and sequencing, secondary structure prediction, alternative splicing analysis Oncogene Medium 1549355

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 356 9927435
2004 The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha. Nature structural & molecular biology 246 15361863
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
2003 A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer research 206 14500382
1997 Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. The Journal of cell biology 198 9024684
2010 Versatile TPR domains accommodate different modes of target protein recognition and function. Cell stress & chaperones 191 21153002
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 179 2052572
2004 Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. The EMBO journal 178 15577939
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
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 160 29432165
2005 Differential control of glucocorticoid receptor hormone-binding function by tetratricopeptide repeat (TPR) proteins and the immunosuppressive ligand FK506. Biochemistry 155 15697228
2007 NUCLEAR PORE ANCHOR, the Arabidopsis homolog of Tpr/Mlp1/Mlp2/megator, is involved in mRNA export and SUMO homeostasis and affects diverse aspects of plant development. The Plant cell 154 17513499
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 153 14574644
1998 Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell stress & chaperones 151 9672247
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 150 11839768
2011 IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. Journal of immunology (Baltimore, Md. : 1950) 144 21813773
2007 From Tpr-Met to Met, tumorigenesis and tubes. Oncogene 143 17322912
2008 Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint. Genes & development 128 18981471
2000 The Nac2 gene of Chlamydomonas encodes a chloroplast TPR-like protein involved in psbD mRNA stability. The EMBO journal 128 10880449
2005 Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein. Molecular cell 113 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
1990 The N-terminal TPR region is the functional domain of SSN6, a nuclear phosphoprotein of Saccharomyces cerevisiae. Molecular and cellular biology 106 2201901
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
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
2020 Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway. Nature communications 95 32917881
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
2015 OsBRI1 Activates BR Signaling by Preventing Binding between the TPR and Kinase Domains of OsBSK3 via Phosphorylation. Plant physiology 91 26697897
1996 Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. The Journal of clinical investigation 90 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
2021 DELLA degradation by gibberellin promotes flowering via GAF1-TPR-dependent repression of floral repressors in Arabidopsis. The Plant cell 84 33822231
2010 Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. The Journal of biological chemistry 80 20133940
2010 AlgK is a TPR-containing protein and the periplasmic component of a novel exopolysaccharide secretin. Structure (London, England : 1993) 80 20159471
2013 Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS neglected tropical diseases 79 23696912
2006 The C-terminal TPR domain of Tom70 defines a family of mitochondrial protein import receptors found only in animals and fungi. Journal of molecular biology 79 16566938
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
2005 Molecular recognition via coupled folding and binding in a TPR domain. Journal of molecular biology 77 15713458
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
2006 Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90. Structure (London, England : 1993) 69 16531226
2011 The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA (New York, N.Y.) 68 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 63 23300914
1999 Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET. Oncogene 62 10435641
2013 Defective nuclear import of Tpr in Progeria reflects the Ran sensitivity of large cargo transport. The Journal of cell biology 58 23649804
2013 Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis. The Journal of cell biology 57 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
1998 Two mutant forms of the S1/TPR-containing protein Rrp5p affect the 18S rRNA synthesis in Saccharomyces cerevisiae. RNA (New York, N.Y.) 52 9848659
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
2012 Regulation of autophagy by nucleoporin Tpr. Scientific reports 46 23170199
2009 Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure. Nature structural & molecular biology 45 19668213
2020 TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes. Nucleic acids research 44 33091126
2019 Architecture of the Cellulose Synthase Outer Membrane Channel and Its Association with the Periplasmic TPR Domain. Structure (London, England : 1993) 43 31604608
2008 Chaperone ligand-discrimination by the TPR-domain protein Tah1. The Biochemical journal 43 18412542
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
2015 MET1 is a thylakoid-associated TPR protein involved in photosystem II supercomplex formation and repair in Arabidopsis. The Plant cell 40 25587003
2005 Proximity of TPR and NTRK1 rearranging loci in human thyrocytes. Cancer research 40 15805251
2020 Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma. Autophagy 36 32207633
2013 Chaperone-interacting TPR proteins in Caenorhabditis elegans. Journal of molecular biology 33 23727266
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 33 23898829
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
2021 The human nucleoporin Tpr protects cells from RNA-mediated replication stress. Nature communications 32 34168151
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
2011 Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells. PloS one 31 21811608
2013 Novel TPR-containing subunit of TOM complex functions as cytosolic receptor for Entamoeba mitosomal transport. Scientific reports 30 23350036
2009 Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr. BMC cell biology 30 19835572
2005 Overexpression of small glutamine-rich TPR-containing protein promotes apoptosis in 7721 cells. FEBS letters 30 15710426
2004 The human small glutamine-rich TPR-containing protein is required for progress through cell division. Experimental cell research 30 14729056
2015 The Non-canonical Tetratricopeptide Repeat (TPR) Domain of Fluorescent (FLU) Mediates Complex Formation with Glutamyl-tRNA Reductase. The Journal of biological chemistry 29 26037924
2005 RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis. Cancer gene therapy 29 15719029
2021 Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. Nature communications 28 33893288
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
2018 Colorectal cancer cells require glycogen synthase kinase-3β for sustaining mitosis via translocated promoter region (TPR)-dynein interaction. Oncotarget 27 29568361
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 Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster. Journal of cell science 27 17878237
2002 Structures and dynamics of Drosophila Tpr inconsistent with a static, filamentous structure. Experimental cell research 26 12027452
1992 Nucleotide sequence analysis of human tpr cDNA clones. Oncogene 26 1549355
2021 Truncation of the TPR domain of OGT alters substrate and glycosite selection. Analytical and bioanalytical chemistry 25 34725712
2020 Cancer-derived UTX TPR mutations G137V and D336G impair interaction with MLL3/4 complexes and affect UTX subcellular localization. Oncogene 25 32071397
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
2012 Structural and thermodynamic characterization of the interaction between two periplasmic Treponema pallidum lipoproteins that are components of a TPR-protein-associated TRAP transporter (TPAT). Journal of molecular biology 25 22504226
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