Affinage

LAMTOR5

Ragulator complex protein LAMTOR5 · UniProt O43504

Length
91 aa
Mass
9.6 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAMTOR5 (HBXIP) is a small Roadblock/LC7-domain protein that adopts a profilin-like fold and dimerizes in solution (PMID:21059355), functioning as both a core lysosomal signaling subunit and a multifunctional oncogenic scaffold/transcriptional co-activator. As a Ragulator subunit, it associates with the complex and is required for amino-acid-dependent mTORC1 activation, with homozygous knockout causing embryonic lethality and ESC self-renewal/differentiation defects that phenocopy other Ragulator subunit losses (PMID:35608036); it physically binds the v-ATPase subunit ATP6V1A to promote V0/V1 holoenzyme assembly and lysosomal acidification, thereby tuning Rag GTPase–mTORC1 coupling, with myeloid-specific loss producing SLE-like disease in mice (PMID:38639386). Through interaction of its leucine-zipper/TIR-like surface with TLR4, LAMTOR5 routes TLR4 to autolysosomal degradation by restraining mTORC1 and de-repressing TFEB, limiting inflammation (PMID:31467416). In its earliest-described role it acts with survivin to bind pro-caspase-9 and block mitochondrial apoptosis (PMID:12773388), and it controls centrosome duplication and bipolar spindle formation, associating with mitotic microtubules (PMID:16982752). A dominant theme across cancer studies is its function as a transcriptional co-activator that directly binds TBP and diverse transcription factors—Sp1, c-Myc, E2F1, STAT4, c-Jun, c-Myb, ETS2, CREB, LXRs, ZNF263—to drive proliferative, metabolic, angiogenic and immune-evasion gene programs (PMID:23494474, PMID:26719542, PMID:26980761, PMID:22740693), recruiting chromatin and modifying machinery such as the Hotair/LSD1 scaffold to c-Myc target genes (PMID:26719542). LAMTOR5 additionally governs protein stability and post-translational modification: it displaces NRF2 from KEAP1 via a GLNLG motif to activate antioxidant ARE signaling (PMID:30692632), directs site-specific acetylation of HMGA2 (K26 via PCAF) and HOXB13 (K277) to block their degradation (PMID:32313942, PMID:29471853), and recruits PKCβII to phosphorylate NMHC-IIA to promote myosin disassembly and migration (PMID:36970214).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 High

    Established the first molecular function of HBXIP—how a small protein could suppress apoptosis—by showing it acts only in complex with survivin rather than alone.

    Evidence Co-IP, complex reconstitution and caspase assays showing survivin-HBXIP (not either alone) binds pro-caspase-9

    PMID:12773388

    Open questions at the time
    • Structural basis of the survivin-HBXIP-procaspase-9 interaction not resolved
    • Did not address whether this role is separable from later scaffold/Ragulator functions
  2. 2006 High

    Defined a cell-cycle function by linking HBXIP to centrosome duplication and bipolar spindle assembly, explaining its requirement for mitotic fidelity and growth.

    Evidence RNAi, overexpression, immunolocalization to mitotic microtubules, and in vivo liver regeneration model

    PMID:16982752

    Open questions at the time
    • Direct molecular partners at the centrosome not identified
    • Mechanism linking centrosome role to its other activities unclear
  3. 2010 High

    Provided the structural foundation, revealing a Roadblock/LC7 profilin-like fold and a dimeric architecture that rationalizes scaffolding and complex membership.

    Evidence 1.5 Å X-ray crystal structure of the 91-aa isoform plus SAXS confirming solution dimer

    PMID:21059355

    Open questions at the time
    • Structures of HBXIP within Ragulator or with transcription-factor partners not determined
    • Functional consequence of dimerization for signaling untested
  4. 2013 High

    Recast HBXIP as a transcriptional co-activator by demonstrating direct TBP binding and promoter occupancy, generalizing a mechanism that would explain its broad gene-activation activity.

    Evidence Co-IP, GST pull-down, ChIP and reporter assays at the Lin28B promoter

    PMID:23494474

    Open questions at the time
    • How HBXIP is recruited to specific promoters genome-wide not defined
    • Stoichiometry within transcription preinitiation complexes unknown
  5. 2015 High

    Showed how HBXIP couples to chromatin-modifying machinery, binding c-Myc via leucine zippers and recruiting the Hotair/LSD1 scaffold to activate c-Myc target genes.

    Evidence Reciprocal Co-IP, ChIP, reporter and in vivo tumor growth assays

    PMID:26719542

    Open questions at the time
    • Direct vs. bridged contact with LSD1 not dissected
    • Generality of Hotair recruitment to other TF partners untested
  6. 2016 High

    Demonstrated a metabolic gene-regulatory role through ligand-independent LXR co-activation feeding a SREBP-1c/FAS lipogenic loop, defining HBXIP as a driver of tumor lipid metabolism.

    Evidence Co-IP, ChIP, reporter, lipogenesis and in vivo tumor assays

    PMID:26980761

    Open questions at the time
    • Structural basis of ligand-independent nuclear-receptor coactivation not resolved
  7. 2019 High

    Identified motif-specific control of protein stability—HBXIP displaces NRF2 from KEAP1 via a GLNLG motif—establishing an antioxidant/ROS-lowering function distinct from its transcriptional role.

    Evidence Co-IP, competitive binding, GLNLG mutagenesis abolishing interaction, ROS and in vivo assays

    PMID:30692632

    Open questions at the time
    • Whether KEAP1 competition is regulated dynamically in cells unknown
  8. 2019 High

    Connected LAMTOR5 to innate immunity by showing it routes TLR4 to autolysosomal degradation through mTORC1 restraint and TFEB de-repression, defining an anti-inflammatory checkpoint.

    Evidence Domain-mapped Co-IP (LZ/TIR), colocalization, TFEB reporter, and haploinsufficient endotoxic-shock mouse model

    PMID:31467416

    Open questions at the time
    • How leucine availability gates this pathway mechanistically not fully resolved
  9. 2020 High

    Resolved a mechanism by which HBXIP stabilizes oncoproteins, directing PCAF-mediated K26 acetylation of HMGA2 to block its ubiquitination and degradation.

    Evidence Co-IP, K26 mutagenesis, Akt-pathway inhibition, ubiquitination and in vivo ESCC assays

    PMID:32313942

    Open questions at the time
    • Whether HBXIP directly contacts PCAF or acts via Akt signaling not fully separated
  10. 2022 High

    Defined LAMTOR5 as a bona fide Ragulator subunit essential for amino-acid-driven mTORC1 activation and embryonic development, anchoring its lysosomal-signaling identity.

    Evidence Co-IP, homozygous knockout (embryonic lethal), and ESC self-renewal/differentiation assays with epistasis to other Ragulator subunits

    PMID:35608036

    Open questions at the time
    • Structural position within Ragulator not defined
    • Relationship between Ragulator role and transcriptional functions unresolved
  11. 2022 High

    Linked LAMTOR5 to cytoskeletal dynamics by direct binding of the NMHC-IIA assembly-competent domain and recruitment of PKCβII to phosphorylate myosin-IIA, explaining a migration-promoting mechanism.

    Evidence MS, Co-IP, GST pull-down, phospho-site mapping (S1916) and in vivo metastasis model

    PMID:36970214

    Open questions at the time
    • How HBXIP couples its scaffolding to kinase recruitment spatially unknown
  12. 2024 High

    Mechanistically tied LAMTOR5 to lysosomal acidification through ATP6V1A binding and v-ATPase holoenzyme assembly, linking its loss to defective mTORC1 control and SLE-like autoimmunity.

    Evidence Co-IP, v-ATPase assembly and acidification assays, myeloid-specific knockout mice, and SLE patient PBMC analysis

    PMID:38639386

    Open questions at the time
    • Structural interface with ATP6V1A not determined
    • How acidification feeds back to its transcriptional functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small Roadblock-domain protein integrates a lysosomal Ragulator/v-ATPase signaling identity with a nuclear transcriptional co-activator identity—what governs its partitioning between these compartments and partners—remains unresolved.
  • No structural model of HBXIP bound to its diverse TF partners
  • Determinants of subcellular partitioning between lysosome and nucleus unknown
  • Whether dimerization switches between functional pools untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005634 nucleus 3 GO:0005764 lysosome 2 GO:0005815 microtubule organizing center 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1 R-HSA-5357801 Programmed Cell Death 1
Partners
ATP6V1AC-MYCKEAP1NMHC-IIAP300SURVIVINTBPTLR4
Complex memberships
Ragulatorsurvivin-HBXIP complexv-ATPase (via ATP6V1A)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 HBXIP functions as a cofactor for survivin: survivin-HBXIP complexes (but neither protein alone) bind pro-caspase-9, preventing its recruitment to Apaf1 and thereby selectively suppressing apoptosis initiated via the mitochondria/cytochrome c pathway. Viral HBx protein also interacts with the survivin-HBXIP complex to suppress caspase activation in a survivin-dependent manner. Co-immunoprecipitation, biochemical complex reconstitution, caspase activity assays The EMBO journal High 12773388
2006 HBXIP is required for bipolar spindle formation and centrosome duplication: HBXIP-deficient cells arrest in prometaphase with monopolar spindles, while HBXIP overexpression causes excessive centrosome replication and tripolar/multipolar spindles. HBXIP associates with microtubules of dividing cells and colocalizes with HBx on centrosomes. HBXIP-deficient cells also fail to complete cytokinesis and undergo apoptosis. In a mouse liver-regeneration model, antisense knockdown of HBXIP impairs hepatocyte growth and survival. RNAi knockdown, overexpression, immunolocalization, fluorescent protein tagging, antisense oligonucleotides in vivo Cancer research High 16982752
2007 The CRHK (residues 137-140) motif in HBx is necessary for binding HBXIP. Mutation of this motif abolishes HBx binding to HBXIP, prevents HBx localization to centrosomes, and abrogates HBx-induced dysregulation of centrosome assembly and modifications of pericentrin and centrin-2. Overexpression of HBXIP or HBXIP fragments that bind HBx neutralizes the effects of viral HBx on centrosome dynamics. Deletion mutagenesis, site-directed mutagenesis, Co-IP, subcellular fractionation, immunofluorescence microscopy The Journal of biological chemistry High 18032378
2007 HBXIP overexpression promotes cell proliferation in MCF-7, H7402, and L-O2 cells, upregulating c-Myc, Bcl-2, and PCNA while downregulating p27. RNAi-mediated knockdown of HBXIP produces opposite effects, demonstrating a role in cell proliferation regulation. Plasmid transfection, RNAi, MTT assay, BrdU incorporation, flow cytometry, Western blot Acta pharmacologica Sinica Medium 17303008
2005 HBXIP interacts with the mitochondrial RNA/DNA helicase hSuv3p. The HBXIP-binding domain identified within hSuv3p is important for mitochondrial import and stability of the Suv3 protein in vivo, suggesting involvement in a survivin-dependent antiapoptotic pathway. Co-immunoprecipitation, deletion analysis, in vivo stability assays The FEBS journal Medium 16176273
2010 Crystal structure of the shortest HBXIP isoform (91 aa) at 1.5 Å resolution reveals a profilin-like fold characteristic of the Roadblock/LC7 domain family. Small-angle X-ray scattering confirms the protein is dimeric in solution, with the dimer interface featuring an extended anti-parallel β-sheet and a small leucine zipper between α2 helices. X-ray crystallography, small-angle X-ray scattering (SAXS) Journal of molecular biology High 21059355
2012 HBXIP up-regulates S100A4 via two pathways: (1) HBXIP directly binds the +200~+239 region of the S100A4 promoter and activates it through interaction with transcription factor STAT4; (2) HBXIP activates PI3K/AKT signaling by inducing DNA methylation of PTEN, which boosts S100A4 expression. Both pathways promote growth and migration of breast cancer cells. ChIP assay, EMSA, co-immunoprecipitation, DNA methylation analysis, luciferase reporter assay, in vitro/in vivo functional assays The Journal of biological chemistry High 22740693
2012 HBXIP upregulates complement regulatory proteins CD46, CD55, and CD59 through activation of p-ERK1/2/NF-κB signaling, protecting breast cancer cells from complement-dependent cytotoxicity. Western blot, siRNA knockdown, luciferase reporter assay, in vivo animal experiments FEBS letters Medium 22293503
2013 HBXIP acts as a co-activator of TF IID by directly binding the TATA-binding protein (TBP): Co-IP and GST pull-down validate direct HBXIP-TBP binding; HBXIP occupies the Lin28B promoter region (-1199/-1073 nt) and transactivates Lin28B expression to promote breast cancer cell proliferation. Co-IP, GST pull-down, ChIP, EMSA, luciferase reporter assay, in vitro/in vivo proliferation assays International journal of cancer High 23494474
2013 HBXIP activates the LMO4 promoter by binding Sp1 at the -237/-206 region containing an Sp1 binding element; mutation of the Sp1 binding site blocks HBXIP-promoter interaction. HBXIP-elevated LMO4 upregulates cyclin D1 and cyclin E, promoting breast cancer cell proliferation. ChIP, EMSA, Co-IP, luciferase reporter assay, flow cytometry, MTT, EdU, xenograft assay Carcinogenesis Medium 23291272
2013 HBXIP upregulates Skp2 by activating the Skp2 promoter (-640/-443 region) through binding E2F1 transcription factor, promoting breast cancer cell proliferation in vitro and in vivo. ChIP, luciferase reporter assay, siRNA knockdown, in vitro/in vivo functional assays Cancer letters Medium 23352642
2014 HBXIP promotes migration of breast cancer cells through the MEKK2/ERK1/2/Capn4 signaling cascade: HBXIP upregulates MEKK2, which activates ERK1/2, which upregulates Calpain small subunit 1 (Capn4), leading to increased filopodia formation and cell migration. Western blot, siRNA knockdown, luciferase reporter assay, immunofluorescence, migration assays Cancer letters Medium 25304384
2014 HBXIP enhances angiogenesis in breast cancer through two pathways: (1) HBXIP directly binds CREB at the FGF8 promoter to upregulate FGF8; (2) HBXIP inhibits miR-503, which directly targets the 3'UTR of FGF8 and VEGF mRNA. HBXIP-induced FGF8 further upregulates VEGF via PI3K/Akt/HIF-1α signaling. ChIP, luciferase reporter assay, Co-IP, siRNA knockdown, Matrigel angiogenesis assay, in vivo hemoglobin content analysis Carcinogenesis Medium 24464787
2015 HBXIP interacts directly with c-Myc through leucine zippers and recruits lncRNA Hotair along with histone demethylase LSD1 (for which Hotair serves as a scaffold) to activate transcription of c-Myc target genes (cyclin A, eIF4E, LDHA) in breast cancer cells. Co-IP, ChIP, luciferase reporter assay, RNAi knockdown, in vitro/in vivo tumor growth assays Cancer research High 26719542
2015 HBXIP upregulates HDAC6 via NF-κB activation, causing HDAC6-mediated deacetylation of MST1 at lysine 35. Deacetylated MST1 interacts with HSC70, leading to lysosome-dependent (chaperone-mediated autophagy) degradation of MST1, reducing Hippo pathway tumor suppressor activity and promoting breast cancer growth. Co-IP, Western blot, trichostatin A treatment, siRNA knockdown, luciferase reporter assay, in vitro/in vivo functional assays Oncogene High 26657153
2015 HBXIP promotes glucose metabolism reprogramming in breast cancer by elevating miR-183/96/182 cluster expression through HIF-1α stabilization: HBXIP disassociates pVHL from HIF-1α to increase HIF-1α stability, and elevated miR-183 further increases HIF-1α by targeting VHL mRNA CDS (forming a feedback loop). miR-183/182 and miR-96 directly inhibit SCO2 and PDHA1 through their coding sequences, switching metabolism from oxidative phosphorylation to aerobic glycolysis. Western blot, Co-IP, luciferase reporter assay, miRNA target validation, metabolic assays (glucose/lactate/ROS), in vivo xenograft Oncotarget Medium 26309161
2015 HBXIP promotes migration of breast cancer cells via GCN5-mediated microtubule acetylation: HBXIP increases α-tubulin acetylation, requires acetyltransferase GCN5 for this effect, and GCN5 is required for HBXIP-enhanced directional cell migration. Immunofluorescence, Western blot, wound-healing assay, siRNA knockdown Biochemical and biophysical research communications Medium 25686500
2016 HBXIP contributes to abnormal lipid metabolism in breast cancer by coactivating nuclear receptors LXRs independent of ligand (via a corepressor/nuclear receptor motif with special flanking sequence), upregulating SREBP-1c (SREBF1), which activates FAS transcription. SREBP-1c in turn activates HBXIP transcription, forming a positive feedback loop (HBXIP→LXR→SREBP-1c→FAS and SREBP-1c→HBXIP). Co-IP, luciferase reporter assay, ChIP, siRNA knockdown, lipogenesis assay, in vitro/in vivo tumor growth assays Cancer research High 26980761
2016 HBXIP suppresses gluconeogenesis in hepatoma cells by inhibiting PCK1 through two mechanisms: (1) upregulation of miR-135a targeting FOXO1 mRNA 3'UTR; (2) activation of PI3K/Akt pathway, increasing FOXO1 phosphorylation and nuclear export, thereby reducing PCK1 transcription. PCK1 overexpression abolishes HBXIP-promoted hepatoma growth. Western blot, luciferase reporter assay, siRNA knockdown, PI3K/Akt pathway inhibition, in vitro/in vivo functional assays Cancer letters Medium 27609066
2016 HBXIP upregulates YAP in hepatoma cells by co-activating transcription factor c-Myb at the YAP promoter. Silencing YAP abolishes HBXIP-mediated hepatoma cell proliferation in vitro and in vivo. ChIP, luciferase reporter assay, Co-IP, siRNA knockdown, in vitro/in vivo proliferation assays Cancer letters Medium 27765671
2017 HBXIP upregulates METTL3 by suppressing miRNA let-7g (which targets METTL3 3'UTR). METTL3 in turn increases HBXIP expression through m6A modification, forming a positive feedback loop (HBXIP→suppression of let-7g→METTL3→m6A modification→HBXIP). This loop promotes breast cancer cell proliferation. Western blot, luciferase reporter assay, m6A modification assay, siRNA knockdown, cell proliferation/apoptosis assays Cancer letters Medium 29174803
2017 TNF-α upregulates HBXIP expression in breast cancer cells via TNFR1: NF-κB and/or p38 signaling activates STAT3, which increases HBXIP promoter activity. HBXIP reciprocally upregulates TNFR1, forming a positive feedback loop (TNFR1→NF-κB/p38→p-STAT3→HBXIP→TNFR1) that promotes breast cancer growth. Western blot, luciferase reporter assay, siRNA knockdown, in vitro/in vivo tumor growth assays Oncotarget Medium 28938560
2017 HBXIP upregulates ACSL1 in breast cancer cells by acting as a coactivator of transcription factor Sp1, binding to the ACSL1 promoter as demonstrated by ChIP assay. Western blot, qRT-PCR, ChIP, luciferase reporter assay, siRNA knockdown Biochemical and biophysical research communications Medium 28132807
2018 HBXIP prevents chaperone-mediated autophagy (CMA)-dependent degradation of HOXB13 by enhancing HOXB13 acetylation at lysine 277, causing HOXB13 protein accumulation. HBXIP also acts as a co-activator of HOXB13 to stimulate IL-6 transcription, promoting tamoxifen resistance in breast cancer. Co-IP, Western blot, luciferase reporter assay, ChIP, site-directed mutagenesis of K277, siRNA knockdown, xenograft assay Journal of hematology & oncology High 29471853
2018 HBXIP modulates the MDM2/p53 feedback loop: HBXIP suppresses miR-18b by inducing DNA methylation of the miR-18b gene, elevating MDM2. HBXIP also promotes MDM2 phosphorylation via activating AKT and directly binds phospho-MDM2, enhancing MDM2-p53 interaction and p53 degradation in breast cancer cells. Western blot, Co-IP, luciferase reporter assay, DNA methylation analysis, siRNA knockdown, in vivo xenograft Acta pharmacologica Sinica Medium 30181579
2018 HBXIP upregulates PKM2 in ER+ breast cancer cells by co-activating E2F1 at the PKM promoter (-779/-579 region), accelerating cell proliferation. ChIP, luciferase reporter assay, Western blot, Co-IP, tissue microarray, xenograft assay Acta pharmacologica Sinica Medium 29925919
2019 LAMTOR5 (HBXIP) regulates TLR4 signaling and inflammation: Lamtor5 associates with TLR4 via their LZ/TIR domains and facilitates colocalization at autolysosomes, preventing lysosomal tethering and mTORC1 activation upon LPS stimulation, thereby de-repressing TFEB to promote autophagic degradation of TLR4. Loss of Lamtor5 leads to sustained inflammation and increased mortality in endotoxic shock mice. Leucine deprivation blunts inflammatory signaling through this Lamtor5-dependent mechanism. Co-IP (LZ/TIR domain interaction), colocalization imaging, TFEB reporter assay, Lamtor5 haploinsufficient mouse model, in vivo endotoxic shock model Cellular & molecular immunology High 31467416
2019 LAMTOR5 stimulates transcription of O-glycosylation enzyme GALNT1 by coactivating c-Jun at the GALNT1 promoter, and triggers dislocation of GALNT1 from the ER via LAMTOR5-dependent activation of c-Src, leading to accumulation of Tn-modified glycoproteins (MUC1, OPN) and promoting breast cancer metastasis. ChIP, luciferase reporter assay, Co-IP, immunofluorescence, Western blot, secondary metastasis mouse model Oncogene High 31836847
2019 HBXIP competitively binds KEAP1 via its conserved GLNLG motif, displacing NRF2 from KEAP1 complexes, promoting NRF2 accumulation and nuclear entry, activating ARE-dependent signaling and reducing intracellular ROS. Mutation of the GLNLG motif abolishes HBXIP-KEAP1 interaction and potently inhibits breast cancer malignancy in vivo and in vitro. Co-IP, competitive binding assay, GLNLG motif mutagenesis, NRF2 nuclear localization assay, ROS measurement, in vitro/in vivo functional assays Oncogene High 30692632
2020 HBXIP induces HMGA2 acetylation at lysine 26 (K26) by activating acetyltransferase PCAF through the Akt pathway (HBXIP→Akt→p-PCAF→PCAF-HMGA2 interaction→K26 acetylation). K26 acetylation enhances HMGA2 DNA binding capacity, blocks ubiquitination, and inhibits proteasomal degradation, stabilizing HMGA2 to promote ESCC growth. Co-IP, site-directed mutagenesis (K26), Western blot, Akt pathway inhibition, ubiquitination assay, in vitro/in vivo functional assays Nucleic acids research High 32313942
2020 HBXIP drives metabolic reprogramming in HCC cells via upregulation of METTL3, which mediates m6A modification of HIF-1α mRNA. METTL3 was shown to physically bind HIF-1α and mediate its m6A modification; HBXIP-mediated METTL3 upregulation restores metabolic reprogramming when HBXIP is partially lost. m6A RNA immunoprecipitation, dot-blot assay, Co-IP (METTL3-HIF-1α binding), Western blot, siRNA knockdown, rescue experiments Journal of cellular physiology Medium 33305825
2021 HBXIP stimulates PD-L1 transcription by co-activating transcription factor ETS2, and induces PD-L1 acetylation at K270 by interacting with acetyltransferase p300, leading to PD-L1 protein stability and promotion of breast cancer growth. Co-IP, ChIP, luciferase reporter assay, RNA-seq, acetylation assay, siRNA knockdown, in vitro/in vivo functional assays Acta pharmacologica Sinica Medium 33824459
2022 HBXIP (LAMTOR5) interacts with the Ragulator complex subunits and is required for mTORC1 activation by amino acids; homozygous knockout of Hbxip in mice causes embryonic lethality with retarded growth at ~E7.5. Hbxip-null ESCs show defects in self-renewal, reduced pluripotency gene expression, and impaired ectodermal/mesodermal differentiation, mirroring phenotypes of Lamtor3 and Lamtor4 knockout ESCs. Co-IP (Ragulator complex interaction), homozygous knockout mouse model, ESC culture/differentiation assays, gene expression analysis, epistasis with other Ragulator subunit knockouts Development (Cambridge, England) High 35608036
2022 HBXIP directly interacts with the assembly-competent domain (ACD) of non-muscle myosin heavy chain IIA (NMHC-IIA) as shown by mass spectrometry, Co-IP, and GST pull-down. HBXIP recruits PKCβII (whose transcription HBXIP induces via Sp1 coactivation), which phosphorylates NMHC-IIA at S1916, enhancing HBXIP-NMHC-IIA interaction and promoting myosin-IIA disassembly, thereby facilitating breast cancer cell migration. Mass spectrometry, Co-IP, GST pull-down, Western blot, phosphorylation assay, RNA-seq, in vivo metastasis model Acta pharmaceutica Sinica. B High 36970214
2022 HBXIP acts as a chaperone of IRE1α (UPR transducer inositol-requiring enzyme 1a) to diminish tamoxifen-induced ER stress in tamoxifen-resistant breast cancer. HBXIP deficiency hyperactivates IRE1α and its downstream pro-apoptotic pathways, and simultaneously induces ROS accumulation that activates PERK and ATF6α branches of the UPR. Co-IP, Western blot, luciferase UPR-element reporter assay, ROS measurement, siRNA knockdown, in vitro/in vivo functional assays The Journal of biological chemistry Medium 35093383
2022 HBXIP prevents sorafenib-induced ferroptosis in HCC by transcriptionally inducing stearoyl-CoA desaturase (SCD) via coactivation of transcription factor ZNF263, resulting in accumulation of free fatty acids and suppression of lipid peroxidation/ferroptosis. ChIP, luciferase reporter assay, Co-IP, malondialdehyde (MDA) measurement, glutathione (GSH) assay, ferroptosis inhibitor rescue, in vitro/in vivo functional assays Acta pharmacologica Sinica Medium 36109580
2024 Lamtor5 is physically associated with ATP6V1A (essential subunit of vacuolar H+-ATPase/v-ATPase) and promotes V0/V1 holoenzyme assembly to facilitate lysosome acidification. Lamtor5 binding to v-ATPase also affects lysosomal tethering of Rag GTPase and weakens Rag GTPase interaction with mTORC1. Loss of Lamtor5 impairs lysosomal function and causes aberrant mTORC1 activation, blunted autolysosomal pathway, and SLE-like manifestations in myeloid-specific knockout mice. Co-IP (Lamtor5-ATP6V1A interaction), v-ATPase assembly assay, lysosome acidification assay, myeloid-specific knockout mouse model, Rag GTPase-mTORC1 interaction assays, analysis of PBMCs from SLE patients Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 38639386
2024 LAMTOR5 silences CHOP expression via two mechanisms: (1) LAMTOR5 recruits DNMT1 to the CpG3 region (-559/-429) of the CHOP promoter to promote DNA hypermethylation, blocking TFII-I binding; (2) LAMTOR5-enhanced miR-182/miR-769 reduce CHOP expression by targeting its 3'UTR. CHOP suppression reduces ER stress-related apoptosis and promotes liver cancer growth. Co-IP (DNMT1 recruitment), ChIP (promoter methylation), DNA methylation assay, luciferase reporter assay, miRNA target validation, siRNA knockdown, in vitro/in vivo functional assays Acta pharmacologica Sinica Medium 38942954
2015 HBXIP modulates the MDM2/p53 feedback loop by directly binding p53 at the P2 promoter of MDM2 and recruiting acetyltransferase p300 to p53 at the MDM2 promoter, increasing MDM2 transcription. Elevated MDM2 enhances p53 degradation, forming an accelerated feedback loop promoting breast cancer growth. Co-IP (HBXIP-p53 and HBXIP-p300 interactions), ChIP, luciferase reporter assay, siRNA knockdown, in vitro/in vivo functional assays The Journal of biological chemistry Medium 26229107
2021 HBXIP promotes NSCLC tumorigenesis by binding MEK1 protein, preventing proteasome-mediated degradation of MEK1 and thereby promoting MAPK/ERK signaling pathway activation. In vivo xenografts confirm HBXIP deficiency decreases MEK1 protein levels and tumor growth. Co-IP, Western blot, immunofluorescence, proteasome inhibition assays, siRNA knockdown, in vivo xenograft Cancer biology & medicine Medium 33628588
2008 HBXIP significantly stimulates hTERT promoter activity and telomerase activity in human mesenchymal stem cells, upregulating hTERT, c-Myc, and Bcl-2 expression, providing a mechanism for HBXIP-promoted cell proliferation. Luciferase reporter assay, TRAP (telomeric repeat amplification protocol), Western blot, RNAi knockdown, plasmid transfection Acta pharmacologica Sinica Medium 18158869

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g. Cancer letters 390 29174803
2003 HBXIP functions as a cofactor of survivin in apoptosis suppression. The EMBO journal 367 12773388
2009 Genome-wide analysis of major intrinsic proteins in the tree plant Populus trichocarpa: characterization of XIP subfamily of aquaporins from evolutionary perspective. BMC plant biology 163 19930558
2015 HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc. Cancer research 115 26719542
2020 HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1α. Journal of cellular physiology 100 33305825
2004 The dual nature of the wheat xylanase protein inhibitor XIP-I: structural basis for the inhibition of family 10 and family 11 xylanases. The Journal of biological chemistry 95 15181003
2016 Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade. Cancer research 83 26980761
2017 Inflammatory factor TNF-α promotes the growth of breast cancer via the positive feedback loop of TNFR1/NF-κB (and/or p38)/p-STAT3/HBXIP/TNFR1. Oncotarget 82 28938560
2000 Interaction of PIP(2) with the XIP region of the cardiac Na/Ca exchanger. American journal of physiology. Cell physiology 82 10751315
2015 Deacetylation of tumor-suppressor MST1 in Hippo pathway induces its degradation through HBXIP-elevated HDAC6 in promotion of breast cancer growth. Oncogene 80 26657153
2006 HBXIP, cellular target of hepatitis B virus oncoprotein, is a regulator of centrosome dynamics and cytokinesis. Cancer research 74 16982752
2022 Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma. Acta pharmacologica Sinica 73 36109580
2002 Interactions defining the specificity between fungal xylanases and the xylanase-inhibiting protein XIP-I from wheat. The Biochemical journal 73 11955286
2012 The oncoprotein HBXIP uses two pathways to up-regulate S100A4 in promotion of growth and migration of breast cancer cells. The Journal of biological chemistry 72 22740693
2012 MicroRNA-501 promotes HBV replication by targeting HBXIP. Biochemical and biophysical research communications 72 23266610
2007 Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation. The Journal of biological chemistry 67 18032378
2018 Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer. Journal of hematology & oncology 65 29471853
2004 XIP-I, a xylanase inhibitor protein from wheat: a novel protein function. Biochimica et biophysica acta 64 14871661
2012 Insights into Populus XIP aquaporins: evolutionary expansion, protein functionality, and environmental regulation. Journal of experimental botany 62 22223812
2020 HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification. Aging 61 33048840
1993 The effect of exchanger inhibitory peptide (XIP) on sodium-calcium exchange current in guinea pig ventricular cells. Circulation research 60 8431979
2013 The oncoprotein HBXIP activates transcriptional coregulatory protein LMO4 via Sp1 to promote proliferation of breast cancer cells. Carcinogenesis 57 23291272
2014 Hepatitis B virus X protein accelerates hepatocarcinogenesis with partner survivin through modulating miR-520b and HBXIP. Molecular cancer 55 24886421
2014 The oncoprotein HBXIP enhances migration of breast cancer cells through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling. Cancer letters 52 25304384
2020 Dynamic Palmitoylation of the Sodium-Calcium Exchanger Modulates Its Structure, Affinity for Lipid-Ordered Domains, and Inhibition by XIP. Cell reports 48 32521252
2014 The oncoprotein HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF. Carcinogenesis 48 24464787
2016 The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to enhance the growth of hepatoma cells. Cancer letters 47 27609066
2017 HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer. Biochemical and biophysical research communications 46 28132807
2015 The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer. Oncotarget 45 26309161
2015 Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin-associated Protein Complexes Using Single Affinity Purification. Molecular & cellular proteomics : MCP 44 26560067
2013 The oncoprotein HBXIP upregulates Lin28B via activating TF II D to promote proliferation of breast cancer cells. International journal of cancer 43 23494474
2012 HBXIP upregulates CD46, CD55 and CD59 through ERK1/2/NF-κB signaling to protect breast cancer cells from complement attack. FEBS letters 43 22293503
2005 A wheat xylanase inhibitor gene, Xip-I, but not Taxi-I, is significantly induced by biotic and abiotic signals that trigger plant defense. Bioscience, biotechnology, and biochemistry 42 15914935
2013 The oncoprotein HBXIP up-regulates Skp2 via activating transcription factor E2F1 to promote proliferation of breast cancer cells. Cancer letters 41 23352642
2012 A novel function for the competence inducing peptide, XIP, as a cell death effector of Streptococcus mutans. FEMS microbiology letters 41 22900705
2019 The oncoprotein HBXIP competitively binds KEAP1 to activate NRF2 and enhance breast cancer cell growth and metastasis. Oncogene 40 30692632
2016 The oncoprotein HBXIP up-regulates YAP through activation of transcription factor c-Myb to promote growth of liver cancer. Cancer letters 40 27765671
2007 Involvement of hepatitis B X-interacting protein (HBXIP) in proliferation regulation of cells. Acta pharmacologica Sinica 39 17303008
2020 The regulation of acetylation and stability of HMGA2 via the HBXIP-activated Akt-PCAF pathway in promotion of esophageal squamous cell carcinoma growth. Nucleic acids research 37 32313942
2019 The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation. Cellular & molecular immunology 34 31467416
2022 HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer. NPJ breast cancer 33 35027562
2005 Human ATP-dependent RNA/DNA helicase hSuv3p interacts with the cofactor of survivin HBXIP. The FEBS journal 33 16176273
2019 LAMTOR5 raises abnormal initiation of O-glycosylation in breast cancer metastasis via modulating GALNT1 activity. Oncogene 32 31836847
2017 The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling. Acta pharmacologica Sinica 32 29188802
2014 The oncoprotein HBXIP up-regulates SCG3 through modulating E2F1 and miR-509-3p in hepatoma cells. Cancer letters 31 24882622
2007 Induction of a novel XIP-type xylanase inhibitor by external ascorbic acid treatment and differential expression of XIP-family genes in rice. Plant & cell physiology 31 17379695
2005 A family 11 xylanase from the pathogen Botrytis cinerea is inhibited by plant endoxylanase inhibitors XIP-I and TAXI-I. Biochemical and biophysical research communications 29 16185656
2012 One if by land, two if by sea: signalling to the ranks with CSP and XIP. Molecular microbiology 27 22958130
2010 Structural characterization of HBXIP: the protein that interacts with the anti-apoptotic protein survivin and the oncogenic viral protein HBx. Journal of molecular biology 27 21059355
2016 Upregulating the Expression of Survivin-HBXIP Complex Contributes to the Protective Role of IMM-H004 in Transient Global Cerebral Ischemia/Reperfusion. Molecular neurobiology 26 26742528
2016 The oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells. Biochemical and biophysical research communications 25 26828265
2015 Fusarium graminearum produces different xylanases causing host cell death that is prevented by the xylanase inhibitors XIP-I and TAXI-III in wheat. Plant science : an international journal of experimental plant biology 25 26475196
2020 HBXIP Regulates Gastric Cancer Glucose Metabolism and Malignancy Through PI3K/AKT and p53 Signaling. OncoTargets and therapy 23 32368094
2023 Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400. The EMBO journal 22 38177313
2015 The oncoprotein HBXIP promotes migration of breast cancer cells via GCN5-mediated microtubule acetylation. Biochemical and biophysical research communications 22 25686500
2011 A new chitinase-like xylanase inhibitor protein (XIP) from coffee (Coffea arabica) affects Soybean Asian rust (Phakopsora pachyrhizi) spore germination. BMC biotechnology 22 21299880
2021 The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth. Acta pharmacologica Sinica 21 33824459
2018 The oncoprotein HBXIP promotes human breast cancer growth through down-regulating p53 via miR-18b/MDM2 and pAKT/MDM2 pathways. Acta pharmacologica Sinica 21 30181579
2017 Intercellular Communication via the comX-Inducing Peptide (XIP) of Streptococcus mutans. Journal of bacteriology 21 28808131
2020 Germacrone Regulates HBXIP-Mediated Cell Cycle, Apoptosis and Promotes the Formation of Autophagosomes to Inhibit the Proliferation of Gastric Cancer Cells. Frontiers in oncology 20 33244453
2015 The oncoprotein HBXIP modulates the feedback loop of MDM2/p53 to enhance the growth of breast cancer. The Journal of biological chemistry 20 26229107
2018 Oncoprotein HBXIP induces PKM2 via transcription factor E2F1 to promote cell proliferation in ER-positive breast cancer. Acta pharmacologica Sinica 19 29925919
2018 The Interaction of lncRNA-HEIH and lncRNA-HULC with HBXIP in Hepatitis B Patients. Gastroenterology research and practice 19 30622563
2019 The oncoprotein HBXIP facilitates metastasis of hepatocellular carcinoma cells by activation of MMP15 expression. Cancer management and research 18 31191014
2018 MiR-145-targeted HBXIP modulates human breast cancer cell proliferation. Thoracic cancer 18 30381907
2017 HBXIP over expression as an independent biomarker for cervical cancer. Experimental and molecular pathology 18 28093193
2013 The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells. Biochemical and biophysical research communications 18 23537647
2007 Identification of multiple highly similar XIP-type xylanase inhibitor genes in hexaploid wheat. Biochemical and biophysical research communications 18 17631271
2021 HBXIP accelerates glycolysis and promotes cancer angiogenesis via AKT/mTOR pathway in bladder cancer. Experimental and molecular pathology 16 34216584
2008 Promotion of cell proliferation by HBXIP via upregulation of human telomerase reverse transcriptase in human mesenchymal stem cells. Acta pharmacologica Sinica 15 18158869
1997 Localization of an exchange inhibitory peptide (XIP) binding site on the cardiac sodium-calcium exchanger. Biochemical and biophysical research communications 15 9223436
2020 The oncogenic role of HBXIP. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 33378953
2019 Oncoprotein LAMTOR5 Activates GLUT1 Via Upregulating NF-κB in Liver Cancer. Open medicine (Warsaw, Poland) 14 30847404
2014 A new cell-penetrating peptide that blocks the autoinhibitory XIP domain of NCX1 and enhances antiporter activity. Molecular therapy : the journal of the American Society of Gene Therapy 14 25582710
2024 Defective Lamtor5 Leads to Autoimmunity by Deregulating v-ATPase and Lysosomal Acidification. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13 38639386
2022 HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis. Acta pharmaceutica Sinica. B 13 36970214
2020 Structure Activity Relationship Study of the XIP Quorum Sensing Pheromone in Streptococcus mutans Reveal Inhibitors of the Competence Regulon. ACS chemical biology 13 32946208
2017 Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP. mSystems 12 28066817
2017 HBXIP, a binding protein of HBx, regulates maintenance of the G2/M phase checkpoint induced by DNA damage and enhances sensitivity to doxorubicin-induced cytotoxicity. Cell cycle (Georgetown, Tex.) 12 28103177
2018 Oncogenic HBXIP enhances ZEB1 through Sp1 to accelerate breast cancer growth. Thoracic cancer 11 30273966
2017 HBXIP overexpression is correlated with the clinical features and survival outcome of ovarian cancer. Journal of ovarian research 11 28388957
2016 The Hevea brasiliensis XIP aquaporin subfamily: genomic, structural and functional characterizations with relevance to intensive latex harvesting. Plant molecular biology 11 27068521
2008 RNAi-mediated knockdown of the XIP-type endoxylanase inhibitor gene, OsXIP, has no effect on grain development and germination in rice. Plant & cell physiology 11 18511458
2016 Suppression of HBXIP Reduces Cell Proliferation, Migration and Invasion In Vitro, and Tumorigenesis In Vivo in Human Urothelial Carcinoma of the Bladder. Cancer biotherapy & radiopharmaceuticals 10 27831760
2021 Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer. Cancer biology & medicine 9 33628588
2022 HBXIP is a novel regulator of the unfolded protein response that sustains tamoxifen resistance in ER+ breast cancer. The Journal of biological chemistry 7 35093383
2022 LncRNA LAMTOR5-AS1 sponges miR-210-3p and regulates cervical cancer progression. The journal of obstetrics and gynaecology research 7 36173004
2021 Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells. Oncology research 7 34588094
2017 HBXIP activates the PPARδ/NF-κB feedback loop resulting in cell proliferation. Oncotarget 7 29416623
2023 HBXIP knockdown inhibits FHL2 to promote cycle arrest and suppress cervical cancer cell proliferation, invasion and migration. Oncology letters 6 37065787
2024 Identification and expression analysis of XIP gene family members in rice. Genetica 5 38743131
2024 HBXIP induces PARP1 via WTAP-mediated m6A modification and CEBPA-activated transcription in cisplatin resistance to hepatoma. Acta pharmacologica Sinica 5 38871923
2024 Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth. Acta pharmacologica Sinica 5 38942954
2022 CRISPR/Cas9-Mediated Disruption of Xylanase inhibitor protein (XIP) Gene Improved the Dough Quality of Common Wheat. Frontiers in plant science 5 35449885
2022 Hbxip is essential for murine embryogenesis and regulates embryonic stem cell differentiation through activating mTORC1. Development (Cambridge, England) 5 35608036
2018 HBXIP regulates etoposide-induced cell cycle checkpoints and apoptosis in MCF-7 human breast carcinoma cells. Gene 5 29309885
2024 Comprehensive genome-wide analysis of wheat xylanase inhibitor protein (XIP) genes: unveiling their role in Fusarium head blight resistance and plant immune mechanisms. BMC plant biology 3 38802731
2009 Algerian pearl millet ( Pennisetum glaucum L.) contains XIP but not TAXI and TLXI type xylanase inhibitors. Journal of agricultural and food chemistry 3 19459708
2021 Down-Regulation of HBXIP Inhibits Non-Small Cell Lung Cancer Growth and Enhances the Anti-Tumor Immunity of Mice by Reducing NRP-1. Annals of clinical and laboratory science 2 34452886
2007 Indirect enzyme-antibody sandwich enzyme-linked immunosorbent assay for quantification of TAXI and XIP type xylanase inhibitors in wheat and other cereals. Journal of agricultural and food chemistry 2 17715986

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