Affinage

KRT8

Keratin, type II cytoskeletal 8 · UniProt P05787

Round 2 corrected
Length
483 aa
Mass
53.7 kDa
Annotated
2026-04-28
130 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KRT8 is a type II simple epithelial keratin that obligatorily heterodimerizes with its type I partner K18 to form tetrameric assembly units that polymerize into intermediate filaments, providing mechanical integrity and organizing the apical membrane domain and microtubule anchoring in simple epithelia (PMID:6186379, PMID:22085677, PMID:11171325). Plectin crosslinks the K8/K18 network at filament intersection points to modulate cytoskeletal stiffness and tether mitochondria for mitophagy, while site-specific phosphorylation—by PKC under mechanical load and by RHOA–PKN at Ser43 under overloading—regulates filament dynamics, autophagosome initiation via RAB33B trafficking, and autophagosome–lysosome fusion (PMID:27489177, PMID:33783309, PMID:36897022, PMID:32022439). KRT8 marks a transitional stem cell state during alveolar regeneration that persists aberrantly in human lung fibrosis, and ectopic TNF-α/NF-κB–driven K8/K18 expression in cardiomyocytes localizes to intercalated discs and confers cardioprotection in the absence of desmin (PMID:32678092, PMID:26280121). In multiple carcinoma contexts, KRT8 promotes epithelial–mesenchymal transition through integrin β1–FAK–TGF-β/SMAD, NF-κB, and RhoA–tight junction signaling axes, and its mRNA stability is regulated by NAT10-mediated ac4C acetylation (PMID:27865045, PMID:29179184, PMID:38922788).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1982 High

    Establishing KRT8 as a distinct type II simple epithelial keratin that forms obligate heteropolymeric filaments with type I partners answered the foundational question of intermediate filament subunit identity and pairing rules in simple epithelia.

    Evidence Two-dimensional gel electrophoresis and immunological characterization across normal epithelia, tumors, and cultured cells

    PMID:6186379

    Open questions at the time
    • Stoichiometry and assembly pathway of heteropolymers not yet defined
    • In vivo requirement for K8/K18 filaments not tested genetically
  2. 1992 Medium

    Demonstrating that PKC selectively phosphorylates K8 over K18 in hepatocytes established that K8 is a regulated signaling target rather than a passive structural scaffold, linking kinase signaling to filament reorganization.

    Evidence Metabolic radiolabeling of TPA-treated primary mouse hepatocytes with immunoprecipitation; PKC down-regulation controls

    PMID:1283312

    Open questions at the time
    • Specific phosphorylation sites on K8 not mapped
    • Functional consequence of phosphorylation on filament mechanics not quantified
  3. 2001 High

    KRT8-knockout mice revealed that K8-based filaments are required for apical membrane protein retention, syntaxin 3 localization, and microtubule anchoring in intestinal enterocytes, establishing K8 as essential for epithelial polarity beyond mechanical support.

    Evidence Analysis of CK8-null mouse intestinal epithelia by immunofluorescence for apical markers, syntaxin 3, γ-tubulin, and microtubules

    PMID:11171325

    Open questions at the time
    • Molecular mechanism linking K8 filaments to syntaxin 3 and γ-tubulin anchoring unknown
    • Whether CFTR mistargeting in KRT8 absence directly drives disease phenotypes not tested
  4. 2011 High

    Biophysical reconstitution of K8/K18 assembly defined the tetramer as the obligate starter unit, measured filament persistence length, and showed Mg²⁺-dependent stiffening, providing the quantitative framework for understanding K8/K18 filament mechanics.

    Evidence Analytical ultracentrifugation, electron microscopy, and persistence length measurements on recombinant K8, K18, and K8/K18 mixtures

    PMID:22085677

    Open questions at the time
    • How post-translational modifications alter assembly kinetics and persistence length not addressed
    • Lateral association mechanism not resolved at atomic level
  5. 2015 High

    HDX-MS mapping of K8/K18 complexes across assembly states provided the first direct structural evidence that IF-consensus motifs at rod-domain termini drive filament elongation via head-to-tail contacts, resolving a long-standing structural question.

    Evidence Hydrogen-deuterium exchange mass spectrometry of recombinant K8/K18 at monomer, tetramer, and filament stages

    PMID:26434626

    Open questions at the time
    • No high-resolution atomic structure of the assembled filament
    • Role of individual head-to-tail contact residues not tested by mutagenesis
  6. 2015 High

    Discovery that TNF-α/NF-κB induces ectopic K8/K18 in desmin-null cardiomyocytes, where the filaments localize to intercalated discs and preserve mitochondrial function, revealed an unexpected cardioprotective role for K8 outside its canonical epithelial context.

    Evidence Desmin-null and aortic constriction mouse models; immunofluorescence and EM of intercalated discs; mitochondrial assays; NF-κB conditional approaches; human failing myocardium

    PMID:26280121

    Open questions at the time
    • Whether K8/K18 expression is a general cardiomyocyte stress response or specific to desmin loss unknown
    • Molecular mechanism of K8/K18 at intercalated discs not defined
  7. 2016 High

    In vitro reconstitution showed plectin crosslinks K8/K18 networks at intersection points without bundling and significantly increases network rigidity, validated by AFM of plectin-depleted epithelial cells, establishing plectin as a major modulator of K8/K18 cytoskeletal mechanics.

    Evidence Reconstituted K8/K18 networks with purified plectin; microrheology; AFM of detergent-extracted A431 cells with plectin siRNA

    PMID:27489177

    Open questions at the time
    • How plectin–K8 interaction is regulated by phosphorylation in cells not tested in this system
    • Other crosslinkers that may cooperate with plectin not identified
  8. 2017 Medium

    Studies in RPE cells and gastric cancer cells converged on the principle that KRT8 phosphorylation state governs a switch between cytoprotective autophagy and pathological EMT, with ERK1/2-mediated phosphorylation promoting EMT through integrin β1–FAK–SMAD2/3 and related signaling axes.

    Evidence Pharmacological autophagy and MAPK modulation in RPE cells; KRT8 overexpression/knockdown with EMT and pathway readouts in gastric cancer cells

    PMID:27865045 PMID:28045574

    Open questions at the time
    • Precise phosphorylation sites driving the autophagy-EMT switch not mapped at this stage
    • Whether the same switch operates in normal epithelia unknown
  9. 2020 High

    Single-cell transcriptomics and lineage tracing identified a Krt8+ transitional stem cell state as a convergent intermediate during alveolar regeneration that persists aberrantly in human lung fibrosis, positioning KRT8 as a marker and potential functional participant in failed regeneration.

    Evidence Time-series scRNA-seq of bleomycin-injured mouse lungs; lineage tracing; trajectory modeling; validation in multiple injury models and human fibrosis tissue

    PMID:32678092

    Open questions at the time
    • Whether KRT8 is functionally required for the transitional state or merely a marker not determined
    • Signals that resolve versus perpetuate the Krt8+ state not identified
  10. 2020 Medium

    Phospho-site mutagenesis showed that phosphorylated KRT8 is required for autophagosome–lysosome fusion during TGF-β2-induced EMT, placing KRT8 phosphorylation as a direct regulator of autophagic flux rather than just filament dynamics.

    Evidence KRT8 phospho-site mutagenesis and siRNA knockdown in RPE cells; autophagy flux and EMT assays

    PMID:32022439

    Open questions at the time
    • Identity of the specific phosphorylation site(s) involved in fusion step not fully resolved
    • Mechanism by which phospho-KRT8 facilitates membrane fusion unknown
  11. 2021 Medium

    KRT8 physically interacts with plectin to tether mitochondria, and oxidative stress–induced KRT8 phosphorylation disrupts this interaction, impairing mitophagy and causing necrotic cell death—directly linking KRT8 phosphorylation to mitochondrial quality control.

    Evidence Reciprocal co-immunoprecipitation of KRT8–plectin; siRNA knockdown; mitochondrial morphology, membrane potential, and mitophagy flux assays in RPE cells

    PMID:33783309

    Open questions at the time
    • Phosphorylation site(s) governing plectin dissociation not mapped
    • Whether this mechanism operates in epithelia beyond RPE not tested
  12. 2023 High

    Identification of Ser43 as the RHOA–PKN phosphorylation site on KRT8 that impedes RAB33B-dependent autophagosome initiation provided the first site-specific mechanistic link between mechanical overloading, KRT8 phosphorylation, and autophagy suppression in intervertebral disc degeneration.

    Evidence Phosphoproteomics; conditional Krt8 knockout and overexpression in nucleus pulposus; in vivo lumbar instability and tail compression models; AAV-mediated gene delivery

    PMID:36897022

    Open questions at the time
    • Whether Ser43 phosphorylation also governs the plectin–KRT8 interaction is untested
    • Structural basis for how pSer43-KRT8 sequesters RAB33B not resolved
  13. 2024 Medium

    NAT10-mediated ac4C modification of KRT8 mRNA was shown to stabilize KRT8 transcript and elevate protein levels driving EMT in prostate cancer, revealing an epitranscriptomic layer of KRT8 regulation beyond transcription and phosphorylation.

    Evidence NAT10 knockdown/overexpression; RNA immunoprecipitation for ac4C-modified KRT8 mRNA; mRNA stability and EMT assays in prostate cancer cells

    PMID:38922788

    Open questions at the time
    • Specific ac4C sites on KRT8 mRNA not mapped
    • Whether ac4C modification of KRT8 mRNA occurs in normal epithelia unknown
  14. 2024 Medium

    TEAD4 was identified as a direct transcriptional regulator of Krt8 in mouse preimplantation embryos, positioning KRT8 downstream of Hippo signaling in trophectoderm specification, though this regulatory relationship is not conserved in bovine embryos.

    Evidence Base editing-mediated Tead4 knockout in mouse embryos; RNA-seq; immunofluorescence for KRT8, CDX2, GATA3, YAP; bovine comparison

    PMID:38206180

    Open questions at the time
    • Whether TEAD4 directly binds the KRT8 promoter (ChIP) not shown
    • Species-specific regulatory logic not explained mechanistically

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: (1) the atomic-resolution structure of the assembled K8/K18 filament, (2) whether KRT8 is functionally required for—or merely marks—the transitional alveolar stem cell state in lung regeneration, and (3) the structural basis by which Ser43 phosphorylation on KRT8 interferes with RAB33B trafficking to suppress autophagosome initiation.
  • No cryo-EM or crystal structure of assembled K8/K18 filament
  • Functional requirement of KRT8 in Krt8+ transitional state not tested by conditional deletion in that lineage
  • Structural mechanism of pSer43-KRT8 interaction with RAB33B unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1500931 Cell-Cell communication 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
KRT18KRT19NAT10PKN1PLECRAB33BTEAD4
Complex memberships
K8/K18 intermediate filament

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1982 KRT8 (cytokeratin 8, a type II keratin) was catalogued as a component of simple epithelial intermediate filaments; it is expressed predominantly in simple and some stratified epithelia and forms obligate heteropolymeric filaments with type I keratin partners. Two-dimensional gel electrophoresis and immunological characterization of keratin proteins from normal epithelia, tumors, and cultured cells Cell High 6186379
1992 CK8 is preferentially phosphorylated over CK18 in primary hepatocytes; treatment with the protein kinase C activator TPA (phorbol ester) induces a transient, sustained increase in CK8 phosphorylation but not CK18 phosphorylation, identifying CK8 as an in vivo substrate of PKC. This phosphorylation was accompanied by cytokeratin aggregate formation in some cells but not wholesale filament disruption. Metabolic radiolabeling of primary mouse hepatocyte cultures treated with TPA, followed by immunoprecipitation and indirect immunofluorescence microscopy; PKC down-regulation experiments Cellular signalling Medium 1283312
1997 In a pancreatic adenocarcinoma model (BSp73), expression of K8 alone stabilized endogenous K19 and enabled keratin filament formation (K8/K19 network), whereas K18 expression was unstable without K8 co-expression. K8/K19-expressing clones retained motility and tumorigenicity, while K18-expressing clones showed dramatically suppressed tumorigenicity and reduced soft-agar growth, indicating that K8 and K18 have opposing roles in regulating cell motility and tumor progression. Stable transfection of K8 and K18 individually and in combination into keratin-null adenocarcinoma cells; soft-agar colony assays, motility assays, syngeneic tumor injection Journal of cell science Medium 9152022
2001 In CK8-null mouse intestinal villus enterocytes (the only cell type lacking IF partners and thus without keratin filaments), apical membrane proteins (alkaline phosphatase, sucrase-isomaltase, CFTR) were progressively lost along the villus, syntaxin 3 was absent, and γ-tubulin mislocalized from its normal sub-apical position with disorganized microtubules. This establishes that the KRT8-based intermediate filament network is required for maintaining the apical membrane domain organization and microtubule anchoring in simple polarized epithelia. Analysis of CK8-knockout mice; immunofluorescence localization of apical markers, syntaxin 3, γ-tubulin, and microtubules in intestinal epithelia and hepatocytes Journal of cell science High 11171325
2011 Recombinant human K8 and K18 assemble into intermediate filaments through a defined pathway: K8 alone forms dimers to tetramers, K18 alone is monomeric, but equimolar K8/K18 mixtures renature as homogeneous tetrameric complexes. These tetramers are the starter units for filament assembly, which proceeds several times faster than vimentin or desmin. The persistence length of K8/K18 filaments is ~300 nm, increasing to ~480 nm with Mg²⁺, indicating Mg²⁺ stiffens the filament by affecting subunit interactions. Analytical ultracentrifugation (sedimentation velocity and equilibrium), electron microscopy of filaments assembled at various protein concentrations and time points, persistence length measurements Journal of structural biology High 22085677
2012 Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells elevates PRL3 (phosphatase of regenerating liver 3) protein levels, which reduces phosphorylation of K8. The resulting stabilized, dephosphorylated K8 promotes increased cell migration, lamellipodia formation, soft-agar colony formation, and metastasis in nude mice. K8/PKP3 double knockdown reversed these phenotypes, placing K8 downstream of PRL3 in a dephosphorylation-dependent mechanism of tumor progression. shRNA knockdown of PKP3 and K8 individually and in combination; Western blotting for PRL3 and phospho-K8; wound-healing and lamellipodia assays; soft-agar colony formation; nude mouse tumorigenesis and metastasis PloS one Medium 22701666
2013 CK8 expression is down-regulated in human intervertebral disc degeneration (IDD) nucleus pulposus (NP) cells. Compressive mechanical loads applied to cultured NP cells cause CK8 phosphorylation and filament disassembly in a time- and magnitude-dependent manner. Protein kinase C (PKC) activation is a critical molecular mediator of compressive load-induced CK8 phosphorylation and downregulation. Western blotting and qRT-PCR of human NP tissue samples; in vitro NP cell compressive loading with pharmacological PKC pathway analysis Laboratory investigation Medium 24166186
2015 TNF-α, acting via NF-κB, drives ectopic expression of keratin 8 (K8) and keratin 18 (K18) in cardiomyocytes of desmin-deficient mice. The ectopic K8/K18 network localizes predominantly to intercalated discs, maintains normal intercalated disc structure and mitochondrial integrity and function, and confers cardioprotection. Loss of the K8/K18 network in this context leads to a maladaptive cardiac phenotype after aortic constriction. Genetic heart failure mouse models (desmin-null and transverse aortic constriction); immunofluorescence and electron microscopy of intercalated discs; mitochondrial function assays; NF-κB reporter and conditional knockout approaches; human failing myocardium immunostaining Nature medicine High 26280121
2015 Hydrogen-deuterium exchange mass spectrometry (HDX-MS) of K8/K18 complexes mapped regions of differential structural dynamics at the tetramer versus filament stages. The IF-consensus motifs at the ends of the central α-helical rod domain, which mediate head-to-tail dimer-dimer interactions, become significantly more protected (less exchangeable) upon filament formation, providing direct structural evidence that these regions drive filament elongation. Homomeric K8 and K18 preparations showed distinct exchange patterns from the heterodimer, revealing partner-dependent stabilization. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) of recombinant K8, K18, and K8/K18 complexes at multiple assembly states (monomer/dimer, tetramer, filament) Journal of structural biology High 26434626
2016 Plectin crosslinks K8/K18 intermediate filament networks at filament intersection points without inducing bundle formation, and plectin-mediated crosslinking increases network rigidity when added at amounts above ~20% of the plectin present in cells. In contrast, potassium ions cause K8/K18 filament bundling that also significantly stiffens the network. In detergent-extracted epithelial cells, downregulation of plectin to ~10% of normal levels significantly decreased cytoskeletal stiffness, establishing plectin as a major modulator of K8/K18 network mechanics. In vitro reconstitution of K8/K18 networks with potassium ions or purified plectin; microrheology; atomic force microscopy of detergent-extracted A431 cells with plectin siRNA knockdown Soft matter High 27489177
2017 KRT8 upregulation following autophagy induction provides a cytoprotective role in retinal pigment epithelium (RPE) cells under oxidative stress. However, phosphorylation of KRT8 (mediated by MAPK1/ERK2 and MAPK3/ERK1) promotes pathological epithelial-mesenchymal transition (EMT) of RPE cells. Inhibition of autophagy further promotes EMT, which can be reversed by MAPK inhibition, establishing a dual role for KRT8 in RPE pathophysiology dependent on its phosphorylation state. RPE cell culture with oxidative stress; pharmacological autophagy inhibition and activation; MAPK1/3 inhibitors; immunofluorescence and Western blotting for phospho-KRT8, EMT markers, and autophagy markers Autophagy Medium 28045574
2017 KRT8 overexpression in gastric cancer cells enhanced proliferation and migration, and was associated with integrin β1-FAK-induced epithelial-mesenchymal transition (EMT) in high-KRT8 cells. KRT8 overexpression increased p-SMAD2/3 levels, linking KRT8 to TGF-β-dependent signaling and EMT. KRT8 siRNA knockdown and overexpression in gastric cancer cell lines; proliferation and migration assays; Western blotting for EMT markers, integrin β1-FAK pathway components, and p-SMAD2/3 Cancer science Medium 27865045
2020 A unique Krt8+ transitional stem cell state arises during alveolar regeneration from both airway and alveolar stem cell lineages converging after lung injury. These Krt8+ cells display squamous morphology, activation of p53 and NF-κB transcriptional programs, and features of cellular senescence. In human lung fibrosis, this Krt8+ transitional state aberrantly persists, establishing a distinct cell-cell communication network with mesenchyme and macrophages. Time-series single-cell RNA-seq of bleomycin-injured mouse lungs; lineage tracing; trajectory modeling; validation in multiple independent lung injury models and human fibrosis samples Nature communications High 32678092
2020 KRT8 phosphorylation correlates with autophagy progression during TGF-β2-induced EMT in retinal pigment epithelial cells. Knockdown of KRT8 or mutagenesis of its critical phosphorylation site impairs autophagosome-lysosome fusion, demonstrating that phosphorylated KRT8 is required for completion of autophagic flux during EMT. siRNA knockdown and phospho-site mutagenesis of KRT8 in RPE cells; TGF-β2-induced EMT; Western blotting and immunofluorescence for autophagy markers and EMT markers; transwell migration assays Journal of cellular and molecular medicine Medium 32022439
2020 Cisplatin upregulates KRT8 in cancer-associated fibroblasts (CAFs), and this KRT8 upregulation suppresses AKT signaling in CAFs, attenuating their ability to promote lung cancer cell migration and invasion. Stimulation of AKT activity (with SC79) reversed KRT8's inhibitory effect on migration, linking KRT8 to suppression of the AKT pathway in CAFs. KRT8 knockdown/overexpression in CAFs; co-culture with lung cancer cells; wound-healing and transwell invasion assays; Western blotting for AKT pathway; nude mouse tumor models OncoTargets and therapy Low 32280245
2020 Analysis of zebrafish periderm enhancers identified a regulatory SNP near the KRT8/KRT18 locus at 12q13 that lies within a periderm enhancer controlling KRT18/KRT8 expression. Reporter assays and deletion analyses confirmed this SNP functionally regulates KRT8/KRT18 expression in periderm cells and is associated with non-syndromic orofacial clefting risk. ATAC-seq on zebrafish periderm and human oral epithelium; gapped-kmer SVM classifiers; reporter assays; CRISPR deletion analysis in zebrafish eLife Medium 32031521
2021 KRT8 physically interacts with the cytolinker protein PLEC (plectin) to tether mitochondria and facilitate mitochondrial fission-mediated mitophagy in RPE cells under oxidative stress. When KRT8 is phosphorylated under oxidative stress conditions, the KRT8-PLEC association is disrupted, impairing mitophagy and leading to accumulation of damaged mitochondria and necrotic cell death. Co-immunoprecipitation to identify KRT8-PLEC interaction; siRNA knockdown of KRT8 and PLEC; mitochondrial morphology and membrane potential assays; mitophagy flux assays; cell death measurements in RPE cells Autophagy Medium 33783309
2022 KRT8 knockdown in lung adenocarcinoma cells suppressed cell proliferation, migration, invasion, and EMT, and significantly inhibited NF-κB signaling, suggesting KRT8 promotes lung carcinogenesis at least in part through NF-κB pathway activation. siRNA knockdown of KRT8 in LUAD cell lines; proliferation, migration, and invasion assays; apoptosis assays; Western blotting for EMT markers and NF-κB pathway components Frontiers in oncology Low 35664775
2023 Phosphorylation of KRT8 at Ser43 by overloading-activated RHOA-PKN (protein kinase N) impedes Golgi-resident RAB33B trafficking, suppressing autophagosome initiation and contributing to intervertebral disc degeneration (IDD). Conditional knockout of Krt8 in nucleus pulposus cells aggravated load-induced IDD in vivo, while Krt8 overexpression conferred protection against overloading-induced apoptosis. Knockdown of Pkn1/Pkn2 at early IDD stages ameliorated disc degeneration. Discovery-driven phosphoproteomics; conditional Krt8 knockout mouse; Krt8 overexpression in NP cells; in vitro compressive loading; in vivo lumbar instability and tail compression models; MRI and histology; AAV-mediated gene delivery Autophagy High 36897022
2024 NAT10 promotes prostate cancer growth and metastasis by acetylating KRT8 mRNA (N4-acetylcytidine, ac4C modification), which increases KRT8 mRNA stability, elevates KRT8 protein levels, and thereby promotes epithelial-mesenchymal transition (EMT) and cell migration. NAT10 knockdown and overexpression; RNA immunoprecipitation (RIP) for ac4C-modified KRT8 mRNA; mRNA stability assays; EMT and migration assays in prostate cancer cell lines Advanced science Medium 38922788
2024 TEAD4 transcriptionally regulates Krt8 expression in mouse preimplantation embryos. TEAD4 knockout by base editing reduces Krt8 expression and causes developmental arrest at the morula stage with dramatic decrease in nuclear YAP in outside cells, placing Krt8 downstream of TEAD4 and upstream of Hippo/YAP signaling in trophectoderm epithelium integrity. This regulatory axis is not conserved in bovine embryos. Base editing-mediated Tead4 knockout in mouse embryos; RNA-seq of knockout embryos; immunofluorescence for KRT8, CDX2, GATA3, and YAP; comparative analysis in bovine embryos Reproduction Medium 38206180
2011 KRT8 haplotype variants are associated with cystic fibrosis disease severity and CFTR-mediated residual chloride secretion in F508del-CFTR homozygotes. One KRT8 haplotype is associated with residual chloride secretion and milder disease, suggesting that KRT8/K18 heterodimeric intermediate filaments are an essential component for proper CFTR apical membrane targeting in epithelial cells. Candidate gene association study with microsatellite and SNP markers in CF patient sibpairs stratified by disease severity and intestinal chloride secretion phenotypes BMC medical genetics Low 21548936
2017 CRF (corticotropin-releasing factor) increases intestinal epithelial permeability by upregulating CK8 expression. CK8 upregulation activates RhoA signaling, promotes actin remodeling, and decreases expression of the tight junction protein ZO-1. CK8 silencing blocked CRF-induced RhoA activation and ZO-1 downregulation but not claudin-1/occludin changes, placing CK8 as a partial mediator between CRF receptor signaling and tight junction regulation. CRF treatment of HT29 intestinal epithelial cells; CK8-silenced cells via shRNA; FITC-dextran permeability assay; transmission electron microscopy of tight junctions; immunoprecipitation for RhoA activity; immunoblotting and immunofluorescence Cellular physiology and biochemistry Medium 29179184
2020 CREB1 transcriptionally suppresses microRNA-186, which in turn targets KRT8 mRNA for degradation. By suppressing miR-186, CREB1 stabilizes KRT8 expression. Elevated KRT8 then increases HIF-1α expression, and HIF-1α blocks the tumor-suppressive effects of CREB1 silencing on gastric cancer cell growth, invasion, and EMT. CREB1 knockdown in gastric cancer cell lines; luciferase reporter assays for miR-186 promoter; miR-186 overexpression; KRT8 overexpression rescue experiments; HIF-1α pathway analysis; proliferation, invasion, and EMT assays Cancer management and research Medium 33061604

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1982 The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 5124 6186379
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nature biotechnology 558 12577067
2020 Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis. Nature communications 542 32678092
2006 New consensus nomenclature for mammalian keratins. The Journal of cell biology 520 16831889
2011 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 507 21565611
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2011 Defining human ERAD networks through an integrative mapping strategy. Nature cell biology 427 22119785
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2020 The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 292 32322062
2006 Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. The International journal of developmental biology 282 16892178
2006 Phosphoproteome analysis of the human mitotic spindle. Proceedings of the National Academy of Sciences of the United States of America 281 16565220
2011 A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 269 21654808
2001 Cell surface heparan sulfate is a receptor for human herpesvirus 8 and interacts with envelope glycoprotein K8.1. Journal of virology 150 11689640
2001 Origin-independent assembly of Kaposi's sarcoma-associated herpesvirus DNA replication compartments in transient cotransfection assays and association with the ORF-K8 protein and cellular PML. Journal of virology 141 11152521
2001 Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells involves heparan sulfate. Journal of virology 124 11462024
1998 The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open reading frame K8.1. Journal of virology 97 9658120
1998 Human herpesvirus-8 ORF K8.1 gene encodes immunogenic glycoproteins generated by spliced transcripts. Virology 87 9740785
2015 Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18. Nature medicine 86 26280121
2004 Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K-bZIP). Virology 86 14972523
2001 Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epithelia. Journal of cell science 86 11171325
2003 Kaposi's sarcoma-associated herpesvirus lytic origin (ori-Lyt)-dependent DNA replication: identification of the ori-Lyt and association of K8 bZip protein with the origin. Journal of virology 84 12719550
1989 Complete nucleotide sequence of the gene encoding VP4 of a human rotavirus (strain K8) which has unique VP4 neutralization epitopes. Journal of virology 84 2474677
2004 K8 and K12 are biotinylated in human histone H4. European journal of biochemistry 81 15153116
2006 Targeted disruption of Kaposi's sarcoma-associated herpesvirus ORF57 in the viral genome is detrimental for the expression of ORF59, K8alpha, and K8.1 and the production of infectious virus. Journal of virology 73 17108026
1999 Characterization of human herpesvirus-8 K8.1A/B glycoproteins by monoclonal antibodies. Virology 73 10489357
2017 High KRT8 expression promotes tumor progression and metastasis of gastric cancer. Cancer science 71 27865045
2010 Detection of antibodies to Kaposi's sarcoma-associated herpesvirus: a new approach using K8.1 ELISA and a newly developed recombinant LANA ELISA. Journal of immunological methods 67 20211626
2017 Autophagy and KRT8/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress. Autophagy 62 28045574
1999 Comparison of human sera reactivities in immunoblots with recombinant human herpesvirus (HHV)-8 proteins associated with the latent (ORF73) and lytic (ORFs 65, K8.1A, and K8.1B) replicative cycles and in immunofluorescence assays with HHV-8-infected BCBL-1 cells. Virology 61 10191203
1999 Identification and characterization of Kaposi's sarcoma-associated herpesvirus K8.1 virion glycoprotein. Journal of virology 55 9882339
1995 Increased expression of cytokeratins CK8 and CK19 is associated with head and neck carcinogenesis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 50 8634660
2002 The human B-cell lymphoma cell line RC-K8 has multiple genetic alterations that dysregulate the Rel/NF-kappaB signal transduction pathway. Oncogene 48 12483529
2004 Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is dispensable for virus entry. Journal of virology 47 15163732
1990 Flow cytometric analysis of DNA content and keratins by using CK7, CK8, CK18, CK19, and KL1 monoclonal antibodies in benign and malignant human breast tumors. Cytometry 47 1696538
1974 Properties of an R plasmid in Pseudomonas aeruginosa producing amikacin (BB-K8), butirosin, kanamycin, tobramycin, and sisomicin resistance. Antimicrobial agents and chemotherapy 47 4217586
2004 Requirement of a 12-base-pair TATT-containing sequence and viral lytic DNA replication in activation of the Kaposi's sarcoma-associated herpesvirus K8.1 late promoter. Journal of virology 43 14963167
2011 Complex formation and kinetics of filament assembly exhibited by the simple epithelial keratins K8 and K18. Journal of structural biology 42 22085677
2007 Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. International immunology 42 17823311
2006 CK8 correlates with malignancy in leukoplakia and carcinomas of the head and neck. Biochemical and biophysical research communications 42 16540085
2001 Human-herpesvirus-8-encoded K8 protein colocalizes with the promyelocytic leukemia protein (PML) bodies and recruits p53 to the PML bodies. Virology 42 11485412
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