Affinage

LRPPRC

Leucine-rich PPR motif-containing protein, mitochondrial · UniProt P42704

Length
1394 aa
Mass
157.9 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRPPRC is a pentatricopeptide repeat (PPR) protein that functions primarily in the mitochondrial matrix as a global post-transcriptional regulator of mitochondrial gene expression. In complex with SLIRP, it acts as an RNA chaperone that stabilizes mitochondrial mRNA secondary structures, promotes polyadenylation, maintains a pool of non-translated mRNAs, and physically delivers mRNAs to the mitoribosome via contacts with mS39 and mS31, with transcript-specific effects most pronounced on COX1 and COX2 (PMID:22045337, PMID:29146908, PMID:39134711). Loss of LRPPRC causes combined OXPHOS deficiency—particularly complex IV and ATP synthase assembly defects—leading to impaired respiration, and biallelic mutations cause Leigh syndrome, French-Canadian type (LSFC), with tissue-specific patterns of OXPHOS dysfunction (PMID:24399447, PMID:25214534, PMID:28575497). Outside mitochondria, LRPPRC participates in PGC-1α coactivator complexes to regulate gluconeogenic and thermogenic gene expression, suppresses autophagy by stabilizing a Bcl-2–Beclin 1 inhibitory complex, and functions as an m6A reader that stabilizes cytoplasmic mRNAs including MDR1, LDHA, and PD-L1 (PMID:17050673, PMID:23822101, PMID:35484333, PMID:37063837).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 Medium

    The initial identification of LRPPRC as a nuclear DNA-binding factor at the MDR1 promoter raised the question of whether it functions in gene regulation beyond mitochondria.

    Evidence EMSA and siRNA knockdown linking LRP130 to invMED1-dependent transcriptional activation of MDR1/MVP

    PMID:15272088

    Open questions at the time
    • Nuclear DNA-binding function not independently replicated
    • Relationship to predominant mitochondrial localization unresolved
    • No structural basis for DNA recognition
  2. 2006 High

    Discovery that LRPPRC is a stable component of the PGC-1α transcriptional coactivator complex established its role in nuclear transcriptional regulation of gluconeogenic and mitochondrial genes, answering how hepatic glucose output is coordinated with mitochondrial biogenesis.

    Evidence Co-IP/mass spectrometry of PGC-1α complex; adenoviral RNAi in fasted mice showing blunted PEPCK/G6P induction

    PMID:17050673

    Open questions at the time
    • Mechanism by which LRPPRC partitions between nucleus and mitochondria unknown
    • Direct vs. indirect effect on PGC-1α target promoters not distinguished
  3. 2010 High

    Definitive localization of LRPPRC to the mitochondrial matrix and demonstration that its loss selectively reduces all mtDNA-encoded mRNAs (but not rRNAs) resolved the primary site of action and established transcript-class specificity.

    Evidence Subcellular fractionation and MTS cleavage analysis; RNAi allelic series with genome-wide expression profiling

    PMID:20220140 PMID:20633537

    Open questions at the time
    • Mechanism of mRNA selectivity over rRNA unknown
    • Whether a dual nuclear-mitochondrial pool exists in vivo remained debated
  4. 2011 High

    Conditional knockout in mouse hearts revealed that LRPPRC maintains a pool of non-translated polyadenylated mRNAs and that its loss abolishes polyadenylation while causing globally dysregulated mitochondrial translation, establishing LRPPRC as a post-transcriptional coordinator rather than simply a stabilizer.

    Evidence Heart-specific Lrpprc KO mice; mRNA polyadenylation assays and metabolic labeling of mitochondrial translation

    PMID:22045337

    Open questions at the time
    • How LRPPRC coordinates polyadenylation machinery mechanistically unclear
    • Transcript-specific translation effects not fully explained
  5. 2012 High

    Mapping of the LRPPRC–COX1 mRNA interaction to the first 19 PPR motifs and a defined mRNA segment provided the first molecular-resolution view of how LRPPRC recognizes its mitochondrial substrates.

    Evidence Recombinant LRPPRC truncations in RNA-binding assays; gene-trap mouse with embryonic lethality and COX deficiency

    PMID:21880015

    Open questions at the time
    • RNA recognition code for individual PPR motifs not decoded
    • Binding to non-COX1 transcripts not mapped at equivalent resolution
  6. 2013 High

    The earlier claim that LRPPRC activates mitochondrial transcription via POLRMT was refuted, firmly placing LRPPRC's function exclusively at the post-transcriptional level.

    Evidence BAC transgenic and heterozygous KO mice; in vitro transcription with purified LRPPRC; size-exclusion chromatography showing no POLRMT interaction

    PMID:23599432

    Open questions at the time
    • Role in precursor RNA processing suggested but not mechanistically defined
  7. 2013 Medium

    Identification of the LRPPRC–Beclin 1–Bcl-2 ternary complex revealed a non-mitochondrial function: LRPPRC suppresses autophagy initiation by maintaining Bcl-2 stability and sequestering Beclin 1.

    Evidence Co-IP of ternary complex; LRPPRC knockdown with LC3-II, p62, and GFP-LC3 puncta readouts

    PMID:23822101

    Open questions at the time
    • Single-lab finding; independent confirmation lacking
    • Whether this occurs at mitochondrial surface or elsewhere is ambiguous
    • Stoichiometry relative to primary mitochondrial RNA function unknown
  8. 2014 High

    Comprehensive OXPHOS phenotyping in LRPPRC-deficient hearts revealed that ATP synthase (complex V) assembly defects—not just COX deficiency—are a major consequence of LRPPRC loss, explaining hyperpolarization and ROS overproduction.

    Evidence Cardiac Lrpprc KO mice; OXPHOS complex activities, membrane potential, and ROS measurements

    PMID:24399447

    Open questions at the time
    • Why ATP synthase is particularly sensitive to LRPPRC loss among OXPHOS complexes not explained
  9. 2014 High

    Analysis of LSFC patient tissues showed that the founder mutation reduces LRPPRC protein in a tissue-specific manner, explaining the tissue-selective pattern of combined complex I+IV deficiency in LSFC.

    Evidence LSFC patient-derived cell lines and tissues; BN-PAGE; OXPHOS complex activity measurements

    PMID:25214534

    Open questions at the time
    • Molecular basis for tissue-specific LRPPRC protein stability not identified
    • Genotype-phenotype correlation for non-founder mutations incomplete
  10. 2015 High

    Slirp knockout mice dissected the division of labor within the LRPPRC–SLIRP complex: SLIRP is dispensable for polyadenylation but required for mRNA association with mitoribosomes, while LRPPRC is essential for both functions.

    Evidence Slirp KO mice; RNA-seq of mitoribosomal fractions; polyadenylation and translation assays

    PMID:26247782

    Open questions at the time
    • How SLIRP facilitates ribosome association mechanistically was unknown
  11. 2016 High

    Structural and mutagenesis studies defined the LRPPRC–SLIRP heterodimer interface, showing that RNA-contacting residues in both proteins are repurposed for protein–protein interaction, explaining the obligate nature of the complex.

    Evidence In vitro reconstitution; mutagenesis of PPR motifs and RRM domain interface residues

    PMID:27353330

    Open questions at the time
    • Full atomic-resolution structure of the heterodimer not determined at this point
    • How RNA binding is accommodated alongside the protein–protein interface unclear
  12. 2017 High

    Transcriptome-wide RNase footprinting and PAR-CLIP demonstrated that LRPPRC–SLIRP is a global RNA chaperone that reshapes the secondary structure of the entire mitochondrial transcriptome, exposing sites for translation, stabilization, and polyadenylation.

    Evidence Deep RNase footprinting combined with PAR-CLIP; LRPPRC loss-of-function analysis

    PMID:29146908

    Open questions at the time
    • Whether chaperone activity is passive (binding-mediated unwinding) or active (ATP-dependent) not resolved
    • Structure-function relationship between individual PPR motifs and transcript regions not defined
  13. 2022 Medium

    Multiple studies identified LRPPRC as an m6A reader that stabilizes cytoplasmic mRNAs (MDR1, PD-L1, CDK6), establishing a post-transcriptional regulatory function for LRPPRC outside mitochondria that links it to chemoresistance, immune evasion, and cell cycle control.

    Evidence RIP and MeRIP-qPCR for m6A-dependent binding to MDR1 and PD-L1 mRNAs; mRNA stability assays; CDK6 mRNA RIP with ChIP showing reciprocal feedback loop

    PMID:35484333 PMID:37063837 PMID:37452037

    Open questions at the time
    • m6A reading domain in LRPPRC not identified structurally
    • Selectivity among m6A-modified transcripts undefined
    • Findings from independent labs but each target studied by a single group
  14. 2022 Medium

    Influenza NS1 protein was shown to competitively displace Beclin 1 from LRPPRC, validating the LRPPRC–Beclin 1 axis as a physiologically targetable autophagy checkpoint exploited by pathogens.

    Evidence Co-IP and competitive binding assays; LRPPRC KO cell lines; autophagy markers during influenza infection

    PMID:36300799

    Open questions at the time
    • Whether other viral proteins exploit the same interface unknown
    • In vivo relevance of this axis during infection not demonstrated
  15. 2024 High

    A cryo-EM structure of the LRPPRC–SLIRP–mRNA–mitoribosome complex revealed the physical mechanism of mRNA delivery: LRPPRC helical repeats contact mS39 and mS31 to form a corridor for mRNA handoff, and mitoribosome profiling confirmed transcript-specific effects on translation, particularly for COX1 and COX2.

    Evidence Cryo-EM structure determination; metabolic labeling; mitoribosome profiling

    PMID:39134711

    Open questions at the time
    • How mRNA is released from LRPPRC into the decoding center not resolved
    • Whether LRPPRC remains associated during elongation or only during initiation unclear
    • Structural basis for transcript-specific translation effects not fully explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for LRPPRC's m6A-reading activity outside mitochondria, the mechanism by which LRPPRC partitions between mitochondrial and extra-mitochondrial pools, and how individual PPR motifs encode transcript selectivity within the mitochondrial transcriptome.
  • No structural model for the m6A-binding interface
  • Dual-localization mechanism undetermined
  • PPR-RNA recognition code for mitochondrial transcript specificity not decoded

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005739 mitochondrion 5 GO:0005634 nucleus 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9612973 Autophagy 3 R-HSA-392499 Metabolism of proteins 2
Partners
BCL2BECN1CDK6MRPS31MRPS39PGC1APRKNSLIRP
Complex memberships
LRPPRC-Beclin 1-Bcl-2 complexLRPPRC-SLIRP heterodimerPGC-1α coactivator complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 LRPPRC forms an RNA-dependent protein complex necessary for maintaining a pool of non-translated mitochondrial mRNAs; loss of LRPPRC decreases mRNA stability, abolishes mRNA polyadenylation, and causes aberrant (misregulated) mitochondrial translation, including excessive translation of some transcripts and no translation of others. Conditional Lrpprc knockout mice (heart-specific); steady-state mRNA analysis, polyadenylation assays, mitochondrial translation assays The EMBO journal High 22045337
2006 LRP130 (LRPPRC) is a component of the PGC-1α transcriptional coactivator holocomplex in the nucleus and regulates expression of gluconeogenic genes (PEPCK, G6P) and certain mitochondrial genes through PGC-1α; adenoviral RNAi knockdown of LRP130 in fasted mice blocks induction of PEPCK and G6P and blunts hepatic glucose output. Co-immunoprecipitation/mass spectrometry of PGC-1α complex; adenoviral RNAi knockdown in mice; gene expression analysis Genes & development High 17050673
2010 LRPPRC is exclusively localized to the mitochondrial matrix in mammalian cells; it is imported into the matrix with cleavage of its mitochondrial targeting sequence upon entry, and orthologous proteins in metazoans all contain mitochondrial targeting signals. Subcellular fractionation, bioinformatic analysis of mitochondrial targeting signals, direct localization experiments in mammalian cells Biochemical and biophysical research communications High 20633537
2010 RNAi-mediated knockdown of LRPPRC specifically reduces steady-state levels of all mitochondrial DNA-encoded mRNAs but not mitochondrial rRNAs, establishing a specific role for LRPPRC in mtDNA-encoded mRNA expression. Stable RNAi knockdown allelic series in cells; genome-wide expression profiling with gene set enrichment analysis The Journal of biological chemistry High 20220140
2017 The LRPPRC–SLIRP complex functions as a global RNA chaperone that stabilizes RNA secondary structures throughout the mitochondrial transcriptome (preferentially mRNAs), exposing sites required for translation, stabilization, and polyadenylation; loss of LRPPRC affects the entire secondary structure and stability of the mitochondrial transcriptome. RNase footprinting combined with PAR-CLIP at high depth; loss-of-function analysis Nature communications High 29146908
2015 SLIRP stabilizes LRPPRC by protecting it from degradation; SLIRP is completely dependent on LRPPRC for its own stability; SLIRP is dispensable for polyadenylation of mtDNA-encoded mRNAs but is required for proper association of mRNAs with the mitochondrial ribosome and efficient translation. Slirp knockout mice; RNA sequencing of mitochondrial ribosomal fractions; molecular analyses of mRNA polyadenylation and translation PLoS genetics High 26247782
2016 LRPPRC and SLIRP form a stable heterodimer via interactions between three neighbouring PPR motifs in the second quarter of LRPPRC and the single RRM domain of SLIRP; residues predicted to contact RNA in both proteins are instead used for protein–protein interactions at the binding interface. In vitro RNA binding assays; mutagenesis of interface residues; biochemical characterization of the heterodimer Nucleic acids research High 27353330
2014 Loss of LRPPRC in conditional knockout mouse hearts causes impaired mitochondrial respiration and reduced ATP production primarily through an ATP synthase (complex V) deficiency, not only COX deficiency; inactive subassembled ATP synthase complexes cause mitochondrial hyperpolarization and increased ROS production. Conditional Lrpprc cardiac knockout mice; measurement of respiratory chain complex activities, ATP production, mitochondrial membrane potential, ROS Human molecular genetics High 24399447
2011 LRP130 (LRPPRC) complexes with the mitochondrial RNA polymerase (POLRMT) to activate mitochondrial transcription, which is associated with increased OXPHOS activity, increased respiratory supercomplexes, denser cristae, and elevated ATP; LRP130 also increases hepatic β-fatty acid oxidation. Genetic and biochemical approaches; co-immunoprecipitation of LRP130 with POLRMT; measurement of OXPHOS activity, ATP, supercomplexes, fatty acid oxidation using 14C-palmitate The Journal of biological chemistry Medium 21971050
2013 LRPPRC does not directly interact with POLRMT or activate mtDNA transcription; variation in LRPPRC levels in vivo affects unprocessed mitochondrial precursor transcripts but not steady-state transcript levels or de novo transcription; LRPPRC acts exclusively as a post-transcriptional regulator. BAC transgenic mice with increased LRPPRC; heterozygous Lrpprc KO mice; size exclusion chromatography; co-immunoprecipitation; in vitro transcription system with purified LRPPRC The Journal of biological chemistry High 23599432
2012 LRPPRC binds directly to a specific segment of COX1 mRNA (mouse mtDNA nucleotides 5961–6020) via its first 19 PPR motifs, and this binding stabilizes mitochondrial mRNA transcripts encoding COX subunits; homozygous LRPPRC disruption causes embryonic lethality and major COX activity decrease in MEFs. Gene-trap mouse model; RNA binding assays with recombinant LRPPRC truncation constructs containing different numbers of PPR motifs; biochemical measurement of respiratory chain complex activities The Biochemical journal High 21880015
2014 LRPPRC forms a ribonucleoprotein complex with SLIRP that stabilizes polyadenylated mitochondrial mRNAs; LSFC founder mutation reduces LRPPRC levels in a tissue-specific manner, leading to tissue-specific patterns of OXPHOS deficiency (combined complex I+IV in muscle, severe complex IV loss in liver). Analysis of LSFC patient-derived cell lines and tissues; BN-PAGE; measurement of OXPHOS complex activities; LRPPRC/SLIRP levels by western blot Human molecular genetics High 25214534
2024 LRPPRC functions as an mRNA delivery factor that recruits mitochondrial mRNAs to the mitoribosome; cryo-EM structure of the LRPPRC–SLIRP–mRNA–mitoribosome complex shows LRPPRC associates with mitoribosomal proteins mS39 and the N-terminus of mS31 through its helical repeats, forming a corridor for mRNA handoff; SLIRP directly binds mRNA and stabilizes LRPPRC; LRPPRC-SLIRP has transcript-specific influence on mRNA translation efficiency, with COX1 and COX2 translation most affected. Cryo-electron microscopy structure determination; RNA sequencing; metabolic labeling; mitoribosome profiling Nature structural & molecular biology High 39134711
2013 LRPPRC associates with mitochondria, interacts with Beclin 1 and Bcl-2, and forms a ternary complex to maintain Bcl-2 stability; suppression of LRPPRC reduces mitochondrial potential and Bcl-2 levels, releasing Beclin 1 to form the Beclin1–PI3KCIII complex and activating autophagy upstream of ATG5-ATG12-mediated LC3-I to LC3-II conversion. Co-immunoprecipitation of LRPPRC–Beclin1–Bcl-2 complex; LRPPRC knockdown in multiple cell lines; autophagy markers (GFP-LC3 puncta, LC3-II, p62); PI3K/Akt/mTOR pathway analysis The Biochemical journal Medium 23822101
2014 LRPPRC maintains the stability of Parkin (which mono-ubiquitinates Bcl-2 to increase Bcl-2 stability and inhibit autophagy); under mitophagy stress, Parkin translocates to mitochondria, binds exposed LRPPRC on ruptured outer mitochondrial membrane, and LRPPRC together with Parkin promotes engulfment of mitochondria into autophagosomes. Co-immunoprecipitation of LRPPRC–Parkin; mitophagy stress assays; immunofluorescence of Parkin translocation PloS one Medium 24722279
2008 LRP130 is a component of PGC-1α coactivator complexes in brown adipocytes; LRP130 is preferentially enriched in brown versus white fat and is induced in a PGC-1-dependent manner during differentiation; brown fat cells deficient for LRP130 show attenuated expression of UCP1 and reduced proton leak. ShRNA knockdown of LRP130 in brown adipocytes; oxygen consumption assays; gene expression analysis; PGC-1α coactivator complex binding The Journal of biological chemistry Medium 18728005
2017 Loss of hepatic LRPPRC causes severe complex IV and ATP synthase assembly defects, impairs long-chain fatty acid oxidation, dysregulates the mitochondrial permeability transition pore, and alters trans-membrane H2O2 diffusion; the H2O2 alteration is traced to ATP synthase assembly defect and changes in mitochondrial membrane lipid composition. Hepatocyte-specific Lrpprc knockout mice; mitochondrial phenotyping including OXPHOS complex activities, ultrastructure, fatty acid oxidation, permeability transition pore assays, ROS measurements Human molecular genetics High 28575497
2004 LRP130 (LRPPRC) binds to the invMED1 cis-activating element in the promoters of MDR1 and MVP genes in the nucleus and is involved in transcriptional activation of these multidrug resistance-related genes; its binding intensity increases with MDR1 expression. Electrophoretic mobility shift assay; siRNA knockdown; transcriptional decoy experiments; nuclear factor identification Nucleic acids research Medium 15272088
2020 LRPPRC forms a transcriptional repressor complex with PGC1α on the FOXO4 promoter; lncRNA GUARDIN acts as a scaffold to stabilize LRP130/PGC1α heterodimers and their occupancy at the FOXO4 promoter, thereby suppressing FOXO4 and p21 expression and preventing cellular senescence. Co-immunoprecipitation of LRP130–PGC1α complex; ChIP at FOXO4 promoter; siRNA knockdown of LRP130/PGC1α; senescence assays EMBO reports Medium 32149459
2022 LRPPRC binds to CDK6 mRNA, increasing its stability and protein expression; CDK6 and its downstream effector E2F1 bind to the LRPPRC promoter and elevate LRPPRC transcription, forming a positive feedback LRPPRC–CDK6 loop that promotes G1/S transition, oxidative phosphorylation, and cancer stem cell generation. RNA immunoprecipitation (RIP) showing LRPPRC–CDK6 mRNA binding; mRNA stability assays; ChIP showing CDK6/E2F1 at LRPPRC promoter; functional cell cycle, OXPHOS, and stem cell assays Nature communications High 37452037
2022 LRPPRC acts as an m6A reader that binds the m6A modification site of MDR1 mRNA and enhances MDR1 mRNA stability and protein expression; P53 normally suppresses LRPPRC via miR-34a; when P53 is mutated, LRPPRC and MDR1 accumulate, promoting chemoresistance. RIP assays; RNA stability assays; miR-34a/LRPPRC/MDR1 pathway analysis; in vitro and in vivo functional assays Cell death and differentiation Medium 35484333
2023 LRPPRC functions as an m6A reader that posttranscriptionally upregulates PD-L1 mRNA stability in an m6A-dependent manner in hepatocellular carcinoma, promoting immune evasion. RIP, MeRIP-qPCR, RNA stability assays, xenograft tumor models, immunohistochemical staining Frontiers in immunology Medium 37063837
2024 LRPPRC promotes glycolysis in triple-negative breast cancer by recognizing the m6A site of LDHA mRNA and enhancing LDHA mRNA stability; LRPPRC knockdown reduces glycolysis while glutaminolysis is enhanced, creating synthetic lethality when combined with glutaminase inhibition. MeRIP-sequencing, RNA-immunoprecipitation, RNA pull-down, RNA stability assays, Seahorse metabolic assays, patient-derived xenografts and organoids Clinical and translational medicine Medium 38372449
2012 LRPPRC associates with HIV-1 nucleic acids during early infection (co-immunoprecipitation RT-PCR); knockdown of LRPPRC reduces preintegration complex formation and viral DNA nuclear import, identifying LRPPRC as a host factor required for early steps of HIV-1 replication. Co-immunoprecipitation RT-PCR; stable LRPPRC knockdown cell lines; subcellular fractionation; viral replication assays PloS one Medium 22808186
2022 Influenza A (H1N1)pdm09 NS1 protein directly interacts with LRPPRC and competitively blocks the interaction of LRPPRC with BECN1, thereby releasing BECN1 to activate PIK3C3 and induce autophagy initiation, promoting viral replication. Co-immunoprecipitation; competitive binding assays; LRPPRC knockout cell lines; autophagy assays Autophagy Medium 36300799
2022 PSMD14 deubiquitinase directly interacts with LRPPRC and inhibits its ubiquitination, thereby stabilizing LRPPRC protein; stabilized LRPPRC in turn suppresses autophagy through the LRPPRC/Beclin1-Bcl-2/SQSTM1 signaling pathway in ovarian cancer. Co-immunoprecipitation of PSMD14–LRPPRC; ubiquitination assays; autophagy marker analysis; in vivo xenograft models Biochimica et biophysica acta. Molecular basis of disease Medium 36328147

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. The Biochemical journal 1718 9716487
1990 Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 1259 2261637
1993 IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science (New York, N.Y.) 675 8511589
1993 LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science (New York, N.Y.) 623 8390097
1997 Signaling mechanisms through gp130: a model of the cytokine system. Cytokine & growth factor reviews 288 9620640
2011 LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. The EMBO journal 280 22045337
2004 Acquiring signalling specificity from the cytokine receptor gp130. Trends in genetics : TIG 247 14698616
2001 Structure of an extracellular gp130 cytokine receptor signaling complex. Science (New York, N.Y.) 222 11251120
2010 gp130 at the nexus of inflammation, autoimmunity, and cancer. Journal of leukocyte biology 209 20610800
1998 Activation of gp130 transduces hypertrophic signals via STAT3 in cardiac myocytes. Circulation 189 9711940
2021 Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting. Journal of cachexia, sarcopenia and muscle 170 34821076
1994 Signal transduction through gp130 that is shared among the receptors for the interleukin 6 related cytokine subfamily. Stem cells (Dayton, Ohio) 168 8075593
2000 Receptor recognition by gp130 cytokines. The EMBO journal 164 10835339
1992 Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. The Journal of biological chemistry 151 1324910
2000 gp130 Cytokine family and bone cells. Cytokine 150 11023660
2020 gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration. Circulation 146 32600062
2007 Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis. Basic research in cardiology 137 17530315
2007 Survival pathways in hypertrophy and heart failure: the gp130-STAT axis. Basic research in cardiology 137 17918316
2008 Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. Journal of immunology (Baltimore, Md. : 1950) 110 18684959
1996 Gp130, a shared signal transducing receptor component for hematopoietic and neuropoietic cytokines. Journal of neurochemistry 109 8666978
2010 GP130 cytokines and bone remodelling in health and disease. BMB reports 106 20797312
2019 LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease. Frontiers in physiology 103 31178748
2021 A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease. Nature 102 33789339
2017 LRPPRC-mediated folding of the mitochondrial transcriptome. Nature communications 100 29146908
2014 Loss of LRPPRC causes ATP synthase deficiency. Human molecular genetics 97 24399447
2006 Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex. Genes & development 86 17050673
2015 SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation. PLoS genetics 82 26247782
2004 Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling. European cytokine network 82 15627637
2003 Lack of gp130 expression in hepatocytes promotes liver injury. Gastroenterology 78 12891556
2016 Bazedoxifene as a Novel GP130 Inhibitor for Pancreatic Cancer Therapy. Molecular cancer therapeutics 75 27535971
2010 Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. The Journal of biological chemistry 74 20220140
2022 Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer. Cell death and differentiation 71 35484333
2004 Shared cytokine signaling receptors: structural insights from the gp130 system. Advances in protein chemistry 69 15500860
2018 Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling but not intracellular autocrine responses. Science signaling 66 30279168
2011 The gp130 receptor cytokine family: regulators of adipocyte development and function. Current pharmaceutical design 64 21375496
2008 GP130-STAT3 regulates epithelial cell migration and is required for repair of the bronchiolar epithelium. The American journal of pathology 61 18467707
2013 Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability. The Biochemical journal 57 23822101
1995 Syp associates with gp130 and Janus kinase 2 in response to interleukin-11 in 3T3-L1 mouse preadipocytes. The Journal of biological chemistry 56 7559603
2014 Epithelial gp130/Stat3 functions: an intestinal signaling node in health and disease. Seminars in immunology 54 24434062
2012 Role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) for anti-apoptosis and tumourigenesis in cancers. European journal of cancer (Oxford, England : 1990) 54 22326293
2009 Cytokine signalling via gp130 in gastric cancer. Biochimica et biophysica acta 54 19665497
1994 Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes. Molecular biology of the cell 54 7812050
2019 Bazedoxifene as a novel GP130 inhibitor for Colon Cancer therapy. Journal of experimental & clinical cancer research : CR 53 30736824
2020 Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. The Journal of experimental medicine 52 31914175
1997 Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase. Journal of immunology (Baltimore, Md. : 1950) 52 9126968
2014 Tissue-specific responses to the LRPPRC founder mutation in French Canadian Leigh Syndrome. Human molecular genetics 50 25214534
2011 LRP130 protein remodels mitochondria and stimulates fatty acid oxidation. The Journal of biological chemistry 50 21971050
2003 The cytokine receptor gp130: faithfully promiscuous. Science's STKE : signal transduction knowledge environment 50 14506288
2008 Modulation of PGC-1 coactivator pathways in brown fat differentiation through LRP130. The Journal of biological chemistry 49 18728005
1995 Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy. Molecular reproduction and development 49 8607969
2021 CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity. JCI insight 46 33986188
2016 The role of gp130 receptor cytokines in the regulation of metabolic homeostasis. The Journal of experimental biology 46 26792338
2016 SLIRP stabilizes LRPPRC via an RRM-PPR protein interface. Nucleic acids research 46 27353330
2010 LRPPRC is a mitochondrial matrix protein that is conserved in metazoans. Biochemical and biophysical research communications 45 20633537
2017 Loss of hepatic LRPPRC alters mitochondrial bioenergetics, regulation of permeability transition and trans-membrane ROS diffusion. Human molecular genetics 43 28575497
2014 Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. PloS one 43 24722279
1998 gp130 and the IL-6 family of cytokines: signaling mechanisms and thrombopoietic activities. Seminars in hematology 43 9685167
2015 Mutations leading to constitutive active gp130/JAK1/STAT3 pathway. Cytokine & growth factor reviews 42 26188635
2010 Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms. Neuropeptides 41 21035185
2023 LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma. Frontiers in immunology 40 37063837
2008 Molecular dissection of gp130-dependent pathways in hepatocytes during liver regeneration. The Journal of biological chemistry 40 18216023
2023 Structural insights into the assembly of gp130 family cytokine signaling complexes. Science advances 39 36930708
2013 The significance of LRPPRC overexpression in gastric cancer. Medical oncology (Northwood, London, England) 38 24375316
2020 GP130 Cytokines in Breast Cancer and Bone. Cancers 37 32023849
2000 Cell density-dependent regulation of hepatic development by a gp130-independent pathway. Biochemical and biophysical research communications 37 11027656
2005 Cross-talk among gp130 cytokines in adipocytes. The Journal of biological chemistry 35 16096272
2014 GP130 activation induces myeloma and collaborates with MYC. The Journal of clinical investigation 34 25384216
2012 LRPPRC mutation suppresses cytochrome oxidase activity by altering mitochondrial RNA transcript stability in a mouse model. The Biochemical journal 34 21880015
2018 Activating mutations of the gp130/JAK/STAT pathway in human diseases. Advances in protein chemistry and structural biology 33 31036294
2008 gp130 signaling in bone cell biology: multiple roles revealed by analysis of genetically altered mice. Molecular and cellular endocrinology 33 18805458
2023 The RNA-binding protein LRPPRC promotes resistance to CDK4/6 inhibition in lung cancer. Nature communications 32 37452037
2022 β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130. Nature metabolism 32 35551509
2017 Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity. Journal of lipid research 32 28874440
2024 Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome. Nature structural & molecular biology 30 39134711
2018 Granulocytes Are Unresponsive to IL-6 Due to an Absence of gp130. Journal of immunology (Baltimore, Md. : 1950) 30 29626088
2016 Transcytosis of IL-11 and Apical Redirection of gp130 Is Mediated by IL-11α Receptor. Cell reports 30 27425614
2009 Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration. Experimental cell research 30 19852956
2013 Targeting gp130 to prevent inflammation and promote insulin action. Diabetes, obesity & metabolism 29 24003934
2004 New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein. Nucleic acids research 28 15272088
2016 Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels. Frontiers in physiology 27 27462273
2013 The leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) does not activate transcription in mammalian mitochondria. The Journal of biological chemistry 27 23599432
2002 A structural template for gp130-cytokine signaling assemblies. Biochimica et biophysica acta 27 12421668
2001 In vitro reconstitution of recognition and activation complexes between interleukin-6 and gp130. Biochemistry 27 11412113
2015 Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model. Cell death & disease 26 25741592
2022 Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC. Biochimica et biophysica acta. Molecular basis of disease 24 36328147
2015 The loss of LRPPRC function induces the mitochondrial unfolded protein response. Aging 24 26412102
2020 Raloxifene inhibits pancreatic adenocarcinoma growth by interfering with ERβ and IL-6/gp130/STAT3 signaling. Cellular oncology (Dordrecht, Netherlands) 23 32940862
2023 A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis. Journal of translational medicine 22 37496051
2022 Inhibition of GP130/STAT3 and EMT by combined bazedoxifene and paclitaxel treatment in ovarian cancer. Oncology reports 22 35029286
2019 Signaling Through gp130 Compromises Suppressive Function in Human FOXP3+ Regulatory T Cells. Frontiers in immunology 22 31379810
2005 Protein phosphatase type 2A, PP2A, is involved in degradation of gp130. Molecular and cellular biochemistry 22 15786731
2024 LRPPRC promotes glycolysis by stabilising LDHA mRNA and its knockdown plus glutamine inhibitor induces synthetic lethality via m6 A modification in triple-negative breast cancer. Clinical and translational medicine 21 38372449
2023 IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models. Science advances 21 37058568
2021 E3 ubiquitin ligase NEDD4L negatively regulates keratinocyte hyperplasia by promoting GP130 degradation. EMBO reports 21 33769697
2014 Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism. Metabolism: clinical and experimental 21 24684823
2014 gp130 in late osteoblasts and osteocytes is required for PTH-induced osteoblast differentiation. The Journal of endocrinology 21 25228504
2020 LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis. EMBO reports 20 32149459
2019 Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma. JCI insight 20 31391340
2012 Knockdown of the cellular protein LRPPRC attenuates HIV-1 infection. PloS one 20 22808186
2022 A/(H1N1) pdm09 NS1 promotes viral replication by enhancing autophagy through hijacking the IAV negative regulatory factor LRPPRC. Autophagy 19 36300799