Affinage

TGFB1I1

Transforming growth factor beta-1-induced transcript 1 protein · UniProt O43294

Length
461 aa
Mass
49.8 kDa
Annotated
2026-04-28
100 papers in source corpus 58 papers cited in narrative 58 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TGFB1I1 (Hic-5/ARA55) is a LIM domain scaffold protein that operates as a signal integrator at the interface of focal adhesion signaling, nuclear receptor transcription, and TGF-β/BMP pathway regulation. At focal adhesions, Hic-5 competitively sequesters FAK from paxillin to inhibit integrin-mediated cell spreading, interacts with PYK2, PTP-PEST, vinculin, GIT1, PINCH–ILK, and tensin1 to regulate adhesion dynamics and ECM organization, and promotes invadopodia formation and fibronectin fibrillogenesis through Src-dependent tyrosine phosphorylation (PMID:11463817, PMID:29348458, PMID:22529104). Hic-5 shuttles to the nucleus via an oxidant-sensitive CRM1-dependent nuclear export signal, where it acts as a ligand-dependent coactivator or corepressor of multiple nuclear receptors (AR, GR, PPARγ, TR4) by scaffolding coactivator complexes (p300, TIF2, Mediator) or blocking chromatin remodeler (CHD9, BRM) access to receptor-occupied sites (PMID:12631731, PMID:16141357, PMID:24591583, PMID:28381557). Hic-5 bidirectionally modulates TGF-β signaling—directly binding and inhibiting Smad3 while promoting Smad7 degradation—and represses BMP-responsive Smads 1/5/8 via its LIM3 domain; through a feed-forward loop with RhoA/ROCK and MRTF-A, it drives mechano-dependent myofibroblast differentiation and fibrosis, as confirmed by attenuated liver and tumor-associated fibrosis in Hic-5 knockout mice (PMID:15561701, PMID:18762808, PMID:21996749, PMID:26759173, PMID:26334580).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 Medium

    Identification of Hic-5 as a TGF-β1- and H2O2-inducible LIM domain gene with growth-inhibitory activity established a new paxillin-family member linking TGF-β signaling to cell growth control.

    Evidence Differential cDNA screening and colony formation assay in fibroblasts

    PMID:7929412

    Open questions at the time
    • Mechanism of growth inhibition undefined
    • No binding partners identified
    • Relationship to paxillin unclear
  2. 1998 High

    Hic-5 was established as a focal adhesion protein that binds FAK and PYK2 via its N-terminal domain and is targeted to focal contacts by its C-terminal LIM domains, defining its dual localization and paxillin-competitive role in integrin signaling.

    Evidence Co-immunoprecipitation, in vitro binding, immunofluorescence across multiple cell types including platelets

    PMID:9422762 PMID:9664039 PMID:9756887

    Open questions at the time
    • Functional consequence of FAK/paxillin competition not yet tested
    • LIM domain DNA-binding significance in vivo unknown
  3. 1999 High

    Hic-5 was identified as a ligand-dependent coactivator of androgen receptor via its LIM domains, revealing an unexpected nuclear receptor coregulatory function for a focal adhesion protein, and PTP-PEST was established as a LIM3 binding partner.

    Evidence Yeast/mammalian two-hybrid, co-IP, reporter assays in DU145 prostate cancer cells; in vitro binding with deletion mutants for PTP-PEST

    PMID:10075738 PMID:10092676

    Open questions at the time
    • Mechanism of nuclear entry undefined
    • Whether coactivation reflects direct chromatin function unknown
  4. 2001 High

    The functional consequence of Hic-5–FAK competition was demonstrated: Hic-5 overexpression sequesters FAK from paxillin, reduces paxillin phosphorylation, and inhibits integrin-mediated cell spreading in a FAK-dependent manner.

    Evidence Overexpression and co-IP in WT vs FAK−/− MEFs, spreading assays on fibronectin, Rac1/Cdc42 rescue

    PMID:11463817

    Open questions at the time
    • Endogenous stoichiometry not addressed
    • In vivo relevance of competitive mechanism unknown
  5. 2003 High

    An oxidant-sensitive CRM1-dependent nuclear export signal was identified in Hic-5, explaining how H2O2 triggers its nuclear accumulation and connecting focal adhesion release (via oxidation of FAK/PTP-PEST binding interfaces) to nuclear gene regulation.

    Evidence NES mutagenesis, leptomycin B treatment, subcellular fractionation, c-fos reporter readout

    PMID:12631731

    Open questions at the time
    • Identity of the nuclear gene program controlled by translocated Hic-5 largely unknown
    • Redox sensor mechanism at molecular detail unresolved
  6. 2005 High

    Hic-5 was shown to function as a true chromatin-level coactivator of GR, recruited to endogenous hormone-responsive promoters in complex with TIF2, p300, and CBP; its depletion reduced coactivator recruitment, and it also served as a PPARγ coactivator directing intestinal epithelial differentiation.

    Evidence ChIP and sequential ChIP at MMTV/c-fos/p21 promoters with RNAi; co-IP and siRNA in gut differentiation model

    PMID:15687259 PMID:16141357

    Open questions at the time
    • Genome-wide scope of coactivation not yet defined
    • How Hic-5 selects between coactivation and corepression at different loci unknown
  7. 2006 High

    Hic-5 was found to homo-oligomerize via LIM4 and hetero-oligomerize with PINCH–ILK, coupling integrin signaling complexes to nuclear shuttling; additionally, Hic-5 was shown to interact with LEF/TCF as a transcriptional repressor.

    Evidence In vitro cross-linking, gel filtration, co-IP, domain mapping, functional growth and reporter assays

    PMID:16291758 PMID:16737959

    Open questions at the time
    • Stoichiometry and dynamics of oligomeric complexes in cells unresolved
    • Physiological significance of LEF/TCF repression untested in vivo
  8. 2008 High

    Hic-5 was established as a bidirectional modulator of TGF-β signaling: it directly binds Smad3 (inhibiting Smad3-dependent transcription) while simultaneously promoting Smad7 degradation to enhance TGF-β signaling; separately, Hic-5 and cyclin D1 compete for CRM1/PINCH-mediated nuclear export, coupling adhesion-dependent ROS to cell cycle control.

    Evidence GST pulldown, co-IP, lentiviral shRNA, PAI-1 reporter; NES mutant and ROS scavenger experiments with PINCH co-IP

    PMID:15561701 PMID:18762808 PMID:18946086

    Open questions at the time
    • Smad7 degradation pathway (non-proteasomal) not molecularly defined
    • How bidirectional Smad regulation is resolved in specific contexts unclear
  9. 2011 High

    Hic-5 and paxillin were shown to have non-redundant roles in 3D migration: Hic-5 depletion induced amoeboid morphology with elevated RhoA/ROCK, while Hic-5 repressed BMP-responsive Smads 1/5/8 via LIM3, expanding its role as a multi-pathway Smad regulator.

    Evidence RNAi in 3D invasion with Rho GTPase activity assays; cell-free GST pulldown for Smad1/5/8 with functional BMP reporter

    PMID:21148292 PMID:21996749

    Open questions at the time
    • In vivo relevance of BMP repression not tested
    • How Hic-5 selectively engages different Smad subsets at endogenous loci unknown
  10. 2014 High

    Genome-wide analysis revealed that Hic-5 acts as a binary switch for GR target gene regulation: at some loci it facilitates Mediator recruitment for activation, while at others it blocks GR occupancy by preventing chromatin remodeling.

    Evidence siRNA depletion, genome-wide expression profiling, ChIP for GR occupancy and chromatin accessibility

    PMID:24591583

    Open questions at the time
    • Identity of chromatin remodelers blocked by Hic-5 not yet determined at this point
    • Structural basis for locus-selective action unknown
  11. 2015 High

    Hic-5 was demonstrated to drive myofibroblast differentiation through a mechanosensitive feed-forward loop with MRTF-A, and Hic-5 knockout mice showed attenuated hepatic fibrosis via Smad7-mediated inhibition of TGF-β/Smad2, validating its pro-fibrotic role in vivo.

    Evidence Hic-5 KO mice with bile duct ligation/CCl4 injury; substrate rigidity manipulation with MRTF-A nuclear translocation imaging; in vivo siRNA

    PMID:26334580 PMID:26759173

    Open questions at the time
    • Whether MRTF-A loop operates in all fibrotic organs untested
    • Direct transcriptional targets of Hic-5/MRTF-A not identified
  12. 2017 High

    The chromatin remodelers CHD9 and BRM were identified as the specific targets blocked by Hic-5 to prevent GR occupancy at 'blocked' loci, resolving the mechanism of Hic-5's gene-selective corepressor activity; separately, Itch E3 ligase was shown to K63-ubiquitinate Hic-5 to restrain its pro-fibrotic activity.

    Evidence Systematic siRNA screen of 11 chromatin remodelers with ChIP for GR occupancy; Itch WT vs C830A rescue and K63-ubiquitination assay

    PMID:28381557 PMID:28612841

    Open questions at the time
    • Whether Hic-5 directly contacts CHD9/BRM or acts through an intermediary unresolved
    • Functional consequences of K63-ubiquitination on Hic-5 localization/stability not fully characterized
  13. 2018 High

    Hic-5 was found to interact with tensin1 in a Src-phosphorylation-dependent and mechanosensitive manner to form fibrillar adhesions, prevent β1 integrin internalization, and promote fibronectin fibrillogenesis in cancer-associated fibroblasts.

    Evidence Co-IP with Src inhibition, integrin trafficking assay, rigidity-dependent fibronectin fibrillogenesis in 2D/3D

    PMID:29348458

    Open questions at the time
    • Which specific Hic-5 tyrosine residues mediate tensin1 binding not mapped
    • Whether tensin1 interaction is required for in vivo tumor stroma organization untested
  14. 2019 Medium

    Hic-5 was shown to be essential for Src-induced invadopodia rosette formation (via FAK kinase activity and LD2/3 motifs) and for maintaining vimentin intermediate filament organization through Cdc42/formin signaling in CAFs.

    Evidence Live imaging, superresolution microscopy, Hic-5 KO CAFs with EGFP-Hic-5 rescue, pharmacological inhibition of Cdc42 and formins

    PMID:30893012 PMID:31644368

    Open questions at the time
    • Direct Hic-5–formin interaction not demonstrated
    • Single lab for vimentin phenotype; independent replication needed
    • How rosette formation connects to in vivo invasion unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for Hic-5's locus-selective chromatin regulation, the identity of the non-proteasomal pathway mediating Hic-5-induced Smad7 degradation, how Hic-5 integrates mechanical and chemical signals to switch between focal adhesion and nuclear functions, and whether Hic-5 has kinase-independent enzymatic activity or acts purely as a scaffold.
  • No high-resolution structure of Hic-5 or its complexes available
  • Non-proteasomal Smad7 degradation mechanism molecularly undefined
  • Integrated mechanotransduction model linking adhesion release to specific nuclear gene programs lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 6 GO:0005856 cytoskeleton 6
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1500931 Cell-Cell communication 3
Partners
FAKGIT1ITCHPINCHPTP-PESTPYK2SMAD3TNS1
Complex memberships
Hic-5/Cbl-c/HSP27Hic-5/MT1-MMP/FAKPINCH-ILK-Hic-5

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Hic-5 (TGFB1I1) is induced by TGF-β1 and H2O2, encodes a protein with four LIM motifs (zinc fingers), and overexpression exerts a cytostatic effect on cellular growth in a cell-type-dependent manner, implicating it in TGF-β1 growth-inhibitory signaling and cellular senescence. Differential cDNA screening, colony formation assay, Northern blot The Journal of biological chemistry Medium 7929412
1997 Forced expression of Hic-5 in immortalized human fibroblasts induces senescence-like phenotypes including growth retardation, increased p21/WAF1/Cip1, and altered extracellular matrix gene expression; antisense Hic-5 delayed senescence in normal diploid fibroblasts. Hic-5 was localized to nuclei and had DNA affinity. Stable transfection with Hic-5 expression vector, antisense RNA expression, immunofluorescence, DNA binding assays Molecular and cellular biology Medium 9032249
1998 Hic-5 localizes to focal adhesions in fibroblasts via its C-terminal LIM domains; the N-terminal domain of Hic-5 directly associates in vitro with the extreme C-terminal region of CAKβ (PYK2), and CAKβ co-immunoprecipitates with Hic-5 from cell lysates. Hic-5 is tyrosine-phosphorylated in Src-transformed cells and in response to osmotic stress. Co-immunoprecipitation, in vitro binding assay, immunofluorescence, Myc-tag localization The Journal of biological chemistry High 9422762
1998 Hic-5 protein binds to focal adhesion kinase (FAK) via its N-terminal domain and is recruited to focal adhesions by its C-terminal LIM domains; overexpression of Hic-5 reduces tyrosine phosphorylation of paxillin, suggesting competitive inhibition. Co-immunoprecipitation, yeast two-hybrid, immunofluorescence, overexpression in COS cells The Journal of biological chemistry High 9756887
1998 The LIM domains of Hic-5 bind DNA in a zinc-dependent manner in vitro; all four LIM domains contribute to DNA binding in distinctive ways, and the protein preferentially binds genomic fragments rich in G+A or with long A/T tracts. In vitro DNA binding assay, immunoprecipitation of protein-DNA complexes, PCR, truncation/domain analysis Nucleic acids research Medium 9722648
1998 Hic-5 is expressed in human platelets instead of paxillin; its LIM domains target GFP to focal contacts, and GST-Hic-5 precipitates FAK and talin from platelet extracts. Cloning from bone marrow cDNA library, GFP targeting assay, GST pulldown from platelet extracts, RT-PCR Journal of cell science Medium 9664039
1999 Hic-5 localizes to focal adhesions and interacts with FAK, FRNK, vinculin, and CSK (but not CRK); focal adhesion targeting is mediated primarily by the LIM domains but sequences outside LIM domains also contribute. Co-immunoprecipitation, immunofluorescence, domain deletion analysis in REF52 cells Journal of cell science High 9858471
1999 Hic-5 interacts with PTP-PEST through its LIM3 domain; PTP-PEST's Pro-2 proline-rich sequence is the binding site on PTP-PEST. This interaction was demonstrated by yeast two-hybrid and in vitro binding with deletion/point mutants. Yeast two-hybrid screening, in vitro binding with deletion/point mutants, co-immunoprecipitation The Journal of biological chemistry High 10092676
1999 Hic-5 functions as a ligand-dependent coactivator of androgen receptor (AR); the C-terminal half containing three LIM motifs is sufficient for AR interaction. Hic-5 enhances AR transcriptional activity in prostate cancer cells in response to DHT and also to antiandrogens such as hydroxyflutamide and 17β-estradiol. Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, transient transfection reporter assay in DU145 cells The Journal of biological chemistry High 10075738
1999 Hic-5 (mammalian ortholog of Drosophila/Lepidoptera DALP) blocks muscle differentiation and induces apoptosis in C2C12 myoblasts when ectopically expressed; these effects are overcome by MyoD expression or contact with normal myoblasts, placing Hic-5 upstream of MyoD. Ectopic expression, C2C12 differentiation assay, epistasis by MyoD co-expression Proceedings of the National Academy of Sciences of the United States of America Medium 10468589
2000 Hic-5 interacts with the tau2 transcriptional activation domain and nuclear matrix-targeting signal of glucocorticoid receptor (GR); a fraction of endogenous Hic-5 associates with the nuclear matrix; the C-terminal LIM domains are required for interactions with focal adhesions, nuclear matrix, and steroid receptors; the N-terminal region harbors a transcriptional activation domain essential for coactivator activity. Yeast two-hybrid, transient transfection reporter assay, biochemical fractionation, indirect immunofluorescence, domain mapping Molecular biology of the cell High 10848625
2000 Hic-5 phosphorylation at tyrosine 60 by CAKβ and Fyn (but not FAK) was established; Y60 phospho-Hic-5 binds specifically to the SH2 domain of Csk; CAKβ-mediated phosphorylation requires both kinase activation and binding of Hic-5 to CAKβ. Overexpression in COS-7 cells, site-directed mutagenesis (Y60F), SH2 domain binding assay, osmotic stress stimulation FEBS letters Medium 10838081
2001 Hic-5 overexpression sequesters FAK from paxillin, reduces tyrosine phosphorylation of paxillin and FAK, and inhibits integrin-mediated cell spreading on fibronectin in a FAK-dependent manner; this inhibition was not observed in FAK-/- MEFs, establishing competitive interference with paxillin–FAK interaction as the mechanism. Overexpression, co-immunoprecipitation, spreading assay on fibronectin, FAK-/- MEFs, dominant-active Rac1/Cdc42 rescue experiments Molecular and cellular biology High 11463817
2001 Hic-5 is identified as an hsp27-binding protein; interaction is mediated by the LIM domains of Hic-5 (specifically LIM4) and the C-terminal domain of hsp27; Hic-5 inhibits hsp27-mediated protection against heat-induced cell death in an interaction-dependent manner. Yeast two-hybrid screen, co-immunoprecipitation, domain mapping with truncation mutants, heat shock survival assay in co-transfected 293T cells The Journal of biological chemistry Medium 11546764
2002 Hic-5 interacts with DAT (dopamine transporter) via the N-terminal intracellular tail of DAT and the LIM region of Hic-5; Hic-5 reduces DAT uptake activity by decreasing cell-surface levels of the transporter; the LIM fragment alone binds DAT but lacks the ability to reduce surface DAT and acts as a dominant negative. Co-immunoprecipitation confirmed endogenous Hic-5–DAT association in brain striatal extracts. Yeast two-hybrid, co-immunoprecipitation from brain striata, surface biotinylation/uptake assay, domain mapping, immunostaining The Journal of neuroscience High 12177201
2002 Hic-5 interacts with GIT1 via its LD3 motif (Hic-5-specific sequence) and the C-terminal paxillin-binding subdomain of GIT1; Hic-5/GIT1 complex contains less PIX than the paxillin/GIT1 complex; GIT1 C-terminal fragment perturbs Hic-5–GIT1 interaction and restores cell spreading inhibited by Hic-5. Yeast two-hybrid, overexpression co-immunoprecipitation, domain mapping, cell spreading assay Journal of biochemistry Medium 12153727
2002 Hic-5 syndesmos (a syndecan-4 cytoplasmic domain interactor) directly binds to Hic-5 and paxillin; this interaction is triggered by protein kinase C activation, connecting syndecan-4 signaling to focal adhesion scaffolds. Yeast two-hybrid, direct binding assay, co-immunoprecipitation The Journal of biological chemistry Medium 11805099
2002 Nuclear Hic-5 transactivates the c-fos promoter through GC/Sp1, Ets, and ERE/AP-1 elements around the −1.3 kb region; Hic-5 does not bind these elements directly but acts as a scaffold in transcriptional complexes involving p300. Luciferase reporter assay, stable transfectants, deletion/point mutant analysis of c-fos promoter Biochemical and biophysical research communications Medium 12445807
2003 Hic-5 accumulates in the nucleus in response to oxidants (H2O2) via an oxidant-sensitive nuclear export signal (NES) located in its N-terminal region; NES consists of a leucine-rich stretch and two cysteines; leptomycin B retains Hic-5 in nucleus; nuclear Hic-5 participates in c-fos gene expression. FAK and PTP-PEST interactions with Hic-5 are sensitive to oxidants and regulate its nuclear translocation. Immunofluorescence, leptomycin B treatment, NES mutation analysis, dominant-negative mutant expression, subcellular fractionation Molecular biology of the cell High 12631731
2004 Hic-5 binds directly to Smad3 through the MH2 domain of Smad3 and the C-terminus (LIM domains) of Hic-5; this interaction inhibits Smad3-dependent TGF-β transcriptional responses (Smad binding element- and PAI-1 promoter-driven reporters) in prostate cell lines; confirmed by GST pulldown in a cell-free system. Co-immunoprecipitation, GST pulldown in cell-free system, luciferase reporter assays, mammalian two-hybrid, domain mapping The Journal of biological chemistry High 15561701
2004 Nuclear Hic-5 transactivates the p21 promoter through two Sp1 sites proximal to the TATA box; this effect is mediated via the Sp1 transactivation domain and functional interaction with p300 through the LIM4 domain of Hic-5; Hic-5 also interacts functionally and physically with Smad3 through its LIM domains to potentiate p21 promoter activity. Reporter assay, GAL4 fusion system, ChIP (chromatin immunoprecipitation), domain deletion analysis Journal of cellular biochemistry Medium 14755691
2004 LIM3 and LIM4 of Hic-5/ARA55 are necessary for maximal GR transactivation; LIM4 functions as a nuclear matrix targeting sequence (NMTS), both necessary and sufficient to target a heterologous protein to the nuclear matrix. Yeast two-hybrid, domain deletion mapping, nuclear matrix targeting assay Journal of cellular biochemistry Medium 15211577
2005 Hic-5/ARA55 is recruited to glucocorticoid-responsive promoters (MMTV, c-fos, p21) in a hormone-dependent manner; Hic-5 associates with GR-containing complexes that also include TIF2, RAC3, CBP, and p300; ablation of Hic-5 reduces TIF2 and p300 recruitment to GR target promoters; Hic-5 also associates with NCoR on GR-responsive promoters in the absence of hormone. Chromatin immunoprecipitation (ChIP) and sequential ChIP, RNA interference knockdown, reporter assay Molecular endocrinology High 16141357
2005 PPARγ interacts with Hic-5; Hic-5 and PPARγ co-localize in gut villus epithelium; Hic-5 enhances PPARγ-mediated induction of intestinal differentiation markers (L-FABP, KLF4, keratin 20); siRNA against Hic-5 reduces PPARγ-mediated gut epithelial gene induction; forced Hic-5 expression during adipocyte differentiation inhibits adipogenesis and induces gut epithelial gene expression. Co-immunoprecipitation, siRNA knockdown, forced expression, reporter assay, ex vivo gut differentiation model Genes & development High 15687259
2005 FAK and PTP-PEST, interacting partners of Hic-5, act as inhibitors of Hic-5 nuclear translocation; interaction of Hic-5 with FAK is regulated by specific cysteines near the binding site and decreases under oxidative conditions; interaction with PTP-PEST is also oxidant-sensitive. Subcellular fractionation, immunofluorescence, co-immunoprecipitation under oxidative conditions, cysteine mutation analysis Antioxidants & redox signaling Medium 15706082
2005 Hic-5 is tyrosine-phosphorylated at residues Y38 and Y60 following EGF treatment; tyrosine-phosphorylated Hic-5 suppresses EGF-induced lamellipodia formation and Rac activation in a focal-adhesion-localization-dependent manner; non-phosphorylatable mutants (Y38F/Y60F) fail to suppress lamellipodia. Site-directed mutagenesis, overexpression in COS-7 cells, Rac activation assay, actin staining Experimental cell research Medium 16183059
2005 Hic-5 is relocalized from focal adhesions to stress fibers through its C-terminal LIM domains during uni-axial cyclic stretch; Hic-5 (unlike paxillin) co-localizes with CRP2 and GIT1 to stress fibers under mechanical stress; Hic-5 suppresses cellular contractility in 3D collagen gels, an effect augmented by CRP2 co-localization. Immunofluorescence during cyclic stretch, domain deletion analysis, 3D collagen gel contraction assay Journal of cell science Medium 15713747
2006 ERK8 interacts with Hic-5 through ERK8's C-terminal-independent region binding to LIM3 and LIM4 domains of Hic-5; ERK8 negatively regulates GRα and AR transactivation mediated by Hic-5 in a kinase-independent manner; ERK8 knockdown enhances dexamethasone-stimulated GR transcriptional activity; regulation of GRα by ERK8 is dependent on Hic-5 presence. Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assay, siRNA knockdown, domain mapping The Journal of biological chemistry Medium 16624805
2006 SERT (serotonin transporter) redistributes between membrane skeleton and cytoskeletal compartments in platelets; Hic-5 interaction with SERT correlates with transporter inactivation and internalization; Hic-5–SERT associations are present in brain synaptosomes; phorbol ester treatment increases Hic-5–SERT interaction and causes SERT internalization. Differential extraction/sedimentation, co-immunoprecipitation, transport activity assay The Journal of biological chemistry Medium 16803896
2006 Hic-5 homo-oligomerizes through its LIM4 domain; Hic-5 (but not paxillin) hetero-oligomerizes with PINCH via LIM4 of Hic-5 and the LIM5 region of PINCH; the Hic-5–PINCH complex also incorporates integrin-linked kinase (ILK); Hic-5 directs PINCH nuclear shuttling only in the presence of ILK; disruption of Hic-5–PINCH hetero-oligomerization impairs cellular growth. Immunoprecipitation, in vitro cross-linking, gel filtration, domain mapping, functional growth assay The Journal of biological chemistry High 16737959
2006 Hic-5 is a LIM C-terminal half-binding protein for LEF/TCF transcription factors (specifically the conserved alternatively spliced exon); HIC-5 acts as a negative regulator of LEF/TCF-activated transcription; LEF/TCF members in turn repress HIC-5-mediated glucocorticoid-driven transcription in a subtype-dependent manner. Yeast two-hybrid, domain mapping, reporter gene assays, Xenopus axis induction assay The Journal of biological chemistry Medium 16291758
2002 Pyk2 directly phosphorylates ARA55/Hic-5 at tyrosine 43, impairing its coactivator activity; Pyk2 also sequesters ARA55, reducing its interaction with androgen receptor; this results in suppression of AR transactivation. Yeast two-hybrid, co-immunoprecipitation, reporter assay, site-directed mutagenesis (Y43) The Journal of biological chemistry Medium 11856738
2003 Dominant-negative ARA55 (dARA55) inhibits AR transcriptional activity and reduces agonist activity of antiandrogens; dARA55 suppresses endogenous ARA55-enhanced AR transactivation by interrupting ARA55 homodimerization; confirmed by siRNA-mediated silencing of ARA55. Inducible expression system, reporter assay, co-immunoprecipitation (dimerization assay), RNA interference Proceedings of the National Academy of Sciences of the United States of America Medium 12700349
2007 Hic-5 is required for TGF-β1-induced EMT; siRNA knockdown of Hic-5 suppresses TGF-β1-induced cell migration, actin stress fiber formation, and E-cadherin down-regulation; Hic-5 knockdown suppresses TGF-β1 induction of RhoA activation; forced Hic-5 expression induces ROCK-dependent actin stress fibers; TGF-β1 induction of Hic-5 is RhoA/ROCK I-dependent, suggesting a feed-forward loop. siRNA knockdown, forced expression, RhoA activity assay, ROCK inhibitor treatment, immunofluorescence Journal of cellular physiology High 17299801
2007 Hic-5 promotes endothelial cell migration toward lysophosphatidic acid (LPA); LPA recruits Hic-5 to focal adhesions and pseudopodia; WT Hic-5 enhances migration via MEK/ERK activation; LIM3 mutant (C369A/C372A) fails to enhance migration, establishing LIM3 dependence; Hic-5 knockdown reduces LPA-stimulated migration. Hic-5 knockdown, overexpression of WT and LIM3 mutant constructs, chemotaxis assay, ERK phosphorylation assay, MEK inhibition American journal of physiology. Heart and circulatory physiology Medium 17337598
2008 Hic-5 directly binds Smad7 via its LIM3 domain; Hic-5 enhances TGF-β signaling by promoting Smad7 protein degradation (non-proteasomal pathway) without reducing Smad7 mRNA; enforced Hic-5 expression reverses Smad7's suppression of Smad 2/3 phosphorylation; lentiviral shRNA silencing of Hic-5 reduces TGF-β responses. Co-immunoprecipitation, direct binding assay, lentiviral shRNA, Western blot for phospho-Smad2/3, PAI-1 reporter assay Oncogene High 18762808
2008 Hic-5 is essential for the pathogenic myofibroblast phenotype in hypertrophic scar fibroblasts; Hic-5 siRNA reduces TGF-β1 production, focal adhesion formation, α-SMA expression, collagen contraction, and ECM synthesis, demonstrating Hic-5 regulates autocrine TGF-β1 production. siRNA knockdown, TGF-β1 ELISA, collagen contraction assay, immunofluorescence, immunoblot The Journal of investigative dermatology Medium 18401422
2008 GnRH receptor signaling induces nuclear translocation of androgen receptor via a pathway involving Pyk2, c-Src, and Hic-5; c-Src phosphorylates Hic-5 and promotes its association with AR; dominant-negative Pyk2 enhanced GnRH-induced AR nuclear translocation; GnRH-induced nuclear AR is transcriptionally inactive, functionally antagonizing testosterone. Co-immunoprecipitation, GFP-AR nuclear translocation imaging, dominant-negative constructs, Pyk2 kinase assay, reporter assay Neuroendocrinology Medium 17202804
2008 Anchorage dependence of cell growth is regulated by competitive nuclear export of cyclin D1 and Hic-5 via CRM1; PINCH serves as an interface for this competition; on loss of adhesion, elevated ROS modifies the Hic-5 NES and stops its nuclear shuttling, retaining cyclin D1 in cytoplasm and inducing p21Cip1-dependent growth arrest. Nuclear export inhibition (leptomycin B), ROS scavengers, ROS-insensitive NES mutant expression, PINCH co-immunoprecipitation, cyclin D1 nuclear localization assay Molecular biology of the cell High 18946086
2011 Paxillin and Hic-5 have distinct roles in breast cancer cell migration through 3D ECMs: paxillin depletion promotes elongated mesenchymal morphology with increased Rac1 activity; Hic-5 depletion induces amoeboid phenotype with elevated RhoA and ROCK-induced myosin II activity; Hic-5 is essential for adhesion formation in 3D environments. RNAi knockdown, 3D invasion assay, Rac1/RhoA activity assay, myosin II inhibition, live imaging Molecular biology of the cell High 21148292
2011 ARA55/Hic-5 functions as a corepressor of TR4 nuclear receptor by recruiting histone acetyltransferase activity to promote TR4 acetylation at K175 and K176 in the DNA-binding domain, reducing TR4 DNA binding and transactivation. Co-immunoprecipitation, acetylation assay, reporter assay, site-directed mutagenesis of acetylation sites The Journal of biological chemistry Medium 21515881
2011 Hic-5 directly binds Smads 1, 5, and 8 via its LIM3 domain and the MH2 domain of those Smads; this interaction represses BMP4 signaling including Id1 induction and BMP-induced apoptosis in prostate cells; Hic-5 silencing enhances endogenous phospho-Smad1/5/8; GST pulldown confirms direct binding in cell-free system. Co-immunoprecipitation, GST pulldown (cell-free), shRNA silencing, reporter assay, domain mapping Oncogene High 21996749
2012 TGF-β-induced Hic-5 up-regulation or ectopic Hic-5 expression promotes invadopodia formation and ECM degradation; Hic-5 is tyrosine-phosphorylated by Src after TGF-β stimulation; non-phosphorylatable Y38/60F mutant inhibits matrix degradation; RhoC (not RhoA) is required for TGF-β and Hic-5-induced matrix degradation; Rac1 regulation of p38 MAPK mediates Hic-5-induced migration in the absence of TGF-β. Src inhibition, overexpression of phosphorylation mutants, Rho GTPase knockdown, in vitro invasion/degradation assay The Journal of cell biology High 22529104
2012 Hic-5 and vinculin interaction is regulated by RhoA activity (in 2D and 3D), while paxillin and vinculin interaction is regulated by Rac1; active vinculin preferentially interacts with Hic-5 in response to RhoA and with paxillin in response to Rac1; Rac1 specifically regulates paxillin and actopaxin dynamics in adhesions. FRET, FRAP, co-immunoprecipitation, active/inactive Rac1/RhoA constructs, 3D matrix analysis PloS one High 22629471
2012 Hic-5 LIM2 domain interacts with the RING finger of Cbl-c through a zinc-coordinating mechanism; this interaction enhances Cbl-c ubiquitin ligase activity after Src phosphorylation/activation and promotes Cbl-c-mediated ubiquitination of EGFR. Co-immunoprecipitation, ubiquitin ligase activity assay, domain mapping with zinc-chelation, EGFR ubiquitination assay PloS one Medium 23145173
2014 Hic-5 depletion selectively affects both activation and repression of GR target genes; for some induced genes Hic-5 facilitates Mediator complex recruitment; for many other genes Hic-5 prevents GR occupancy and chromatin remodeling, thereby inhibiting hormone-dependent regulation (acting as an 'on/off switch'). siRNA depletion, genome-wide gene expression analysis, ChIP for GR occupancy and chromatin remodeling Proceedings of the National Academy of Sciences of the United States of America High 24591583
2014 Hic-5 associates with ubiquitin ligase Cbl-c and ubiquitin-binding protein HSP27; this trimeric interaction is required for ubiquitination of Nox4 and its proteasomal degradation; Hic-5 silencing induces constitutive Nox4 expression by blocking this ubiquitin-proteasomal degradation pathway; this positions Hic-5 as a negative feedback regulator of myofibroblast differentiation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, proteasome inhibitor treatment The Journal of biological chemistry Medium 24831009
2014 Hic-5 rapidly translocates to the nucleus upon androgen stimulation in prostate myofibroblasts, coincident with increased FAK phosphorylation; as a coregulator Hic-5 amplifies or inhibits approximately 50% of AR target genes genome-wide. Live cell imaging of nuclear translocation, genome-wide expression analysis after Hic-5 depletion, ChIP Molecular and cellular endocrinology Medium 24440747
2015 Hic-5 deficiency attenuates hepatic stellate cell (HSC) activation and liver fibrosis; mechanistically, Hic-5 absence inhibits TGF-β/Smad2 signaling by upregulating Smad7, resulting in reduced collagen and α-SMA in activated HSCs; established in both Hic-5 KO mice and siRNA in vivo. Hic-5 KO mouse model, bile duct ligation and CCl4 injury, siRNA in vivo, Western blot for Smad2/Smad7, immunohistochemistry Journal of hepatology High 26334580
2015 Hic-5 is required for mechanically dependent stress fiber generation and MRTF-A nuclear accumulation in response to TGF-β; Hic-5 is required for α-SMA induction and cellular contractility; MRTF-A localization by Hic-5 and Hic-5 expression by MRTF-A form a mechanically dependent feed-forward loop for myofibroblast differentiation. siRNA knockdown, forced expression, substrate rigidity manipulation, MRTF-A nuclear localization imaging, α-SMA induction, contractility assay Journal of cell science High 26759173
2015 Hic-5 mediates endothelial sprouting initiation by forming a complex with MT1-MMP via its LIM2 and LIM3 domains; this complex is enriched in detergent-resistant membrane fractions; Hic-5 depletion lowers surface MT1-MMP levels; Hic-5 also bridges MT1-MMP and FAK; the Hic-5/MT1-MMP/FAK complex is present in angiogenic vessels in vivo. siRNA knockdown, rescue by re-expression, co-immunoprecipitation, domain mapping (LIM2/LIM3 deletion mutants), surface protein assay, immunostaining of porcine pregnancy vasculature Journal of cell science High 26769900
2015 TGF-β-induced Hic-5 expression and interaction with HSP27 is required for Hic-5 localization to focal adhesions; Hic-5 expression is required for TGF-β-mediated increases in focal adhesion number, adhesive force, and migration in vascular smooth muscle cells; Nox4 downregulation impedes Smad signaling and blocks Hic-5 upregulation; Hic-5 is downstream of Nox4/Smad4. Molecular biology techniques, co-immunoprecipitation, Nox4 siRNA, Smad4-deficient cells, traction force microscopy/adhesion assay Arteriosclerosis, thrombosis, and vascular biology Medium 25814672
2016 In PyMT breast cancer mouse model, Hic-5 is primarily expressed in cancer-associated fibroblasts (CAFs); Hic-5-/-;PyMT mice have fewer CAFs, reduced ECM deposition, reduced tumor stroma rigidity, and decreased FAK Y397 phosphorylation in tumor cells; isolated Hic-5-/- CAFs show defective stress fiber organization, reduced contractility, and failure to deposit/organize ECM. Hic-5 KO mouse crossed with PyMT model, immunohistochemistry, isolated CAF assays, 2D/3D ECM organization assay Oncogene High 27893716
2017 Hic-5 blocks GR binding to a subset of gene regulatory sites by selectively inhibiting GR interaction with chromatin remodeling ATPases CHD9 and BRM (SMARCA2); CHD9 and BRM are required for GR occupancy at 'blocked' gene loci but not at other GR target sites; Hic-5 selectively inhibits GR-CHD9 and GR-BRM interactions. Depletion of 11 chromatin remodelers by siRNA, ChIP for GR occupancy, chromatin remodeling assay, co-immunoprecipitation The Journal of biological chemistry High 28381557
2017 Itch E3 ubiquitin ligase directly binds HIC-5 and targets it for K63-linked ubiquitination; reconstitution with WT Itch but not catalytic mutant (C830A) normalizes IL-17-driven profibrotic gene expression; shRNA inhibition of HIC-5 normalizes profibrotic gene expression in Itch-/- myofibroblasts, placing HIC-5 downstream of Itch in intestinal fibrosis regulation. Co-immunoprecipitation, ubiquitination assay, rescue with Itch WT vs C830A mutant, shRNA knockdown Mucosal immunology Medium 28612841
2018 Hic-5 promotes fibrillar adhesion formation in CAFs through a newly characterized interaction with tensin1; Src-dependent phosphorylation of Hic-5 facilitates the Hic-5–tensin1 interaction to prevent β1 integrin internalization and lysosomal trafficking; this interaction is mechanosensitive and promotes fibronectin fibrillogenesis in a rigidity-dependent manner. Co-immunoprecipitation, Src inhibition, fibrillar adhesion assay, integrin trafficking assay, 2D/3D fibronectin fibrillogenesis, rigidity manipulation Oncogene High 29348458
2019 Hic-5 is essential for Src-induced invadopodia rosette formation; FAK kinase activity plus proximity to LD2,3 motifs of Hic-5 is necessary for rosette formation; Rac1, formin, and myosin II activity are required for rosette dynamics; superresolution microscopy revealed formin FHOD1 and INF2-mediated radial F-actin fibers from rosettes. Live cell imaging, domain mapping, pharmacological inhibition (FAK, Rac1, formin, myosin II), superresolution microscopy, Hic-5 KO CAFs Molecular biology of the cell Medium 30893012
2019 Hic-5 genetic ablation in CAFs promotes collapse of the vimentin intermediate filament network; vimentin collapse correlates with loss of soluble vimentin precursors and decreased vimentin S72/S82 phosphorylation; Cdc42 inhibition rescues vimentin collapse in Hic-5 KO CAFs; pan-formin inhibition reproduces vimentin collapse, placing Hic-5 upstream of Cdc42 and formin-mediated vimentin organization. Hic-5 KO CAFs, EGFP-Hic-5 rescue, FRAP of vimentin dynamics, Cdc42 inhibition, SMIFH2 formin inhibition, Western blot Molecular biology of the cell Medium 31644368

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. The Journal of biological chemistry 233 10075738
1994 Characterization of the TGF beta 1-inducible hic-5 gene that encodes a putative novel zinc finger protein and its possible involvement in cellular senescence. The Journal of biological chemistry 170 7929412
2011 Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis. Molecular biology of the cell 147 21148292
1999 Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin. Journal of cell science 137 9858471
2012 Hic-5 promotes invadopodia formation and invasion during TGF-β-induced epithelial-mesenchymal transition. The Journal of cell biology 131 22529104
2000 Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix. Molecular biology of the cell 114 10848625
1998 Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions. The Journal of biological chemistry 114 9422762
2005 Hic-5 regulates an epithelial program mediated by PPARgamma. Genes & development 89 15687259
2007 Hic-5 contributes to epithelial-mesenchymal transformation through a RhoA/ROCK-dependent pathway. Journal of cellular physiology 88 17299801
2006 Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter. The Journal of biological chemistry 86 16803896
1997 Induction of senescence-like phenotypes by forced expression of hic-5, which encodes a novel LIM motif protein, in immortalized human fibroblasts. Molecular and cellular biology 86 9032249
2001 Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase. Molecular and cellular biology 85 11463817
2002 The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter. The Journal of neuroscience : the official journal of the Society for Neuroscience 84 12177201
2003 Hic-5 communicates between focal adhesions and the nucleus through oxidant-sensitive nuclear export signal. Molecular biology of the cell 80 12631731
1999 Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase PEST (PTP-PEST) through its LIM 3 domain. The Journal of biological chemistry 80 10092676
1998 Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase. The Journal of biological chemistry 79 9756887
2008 Hic-5 promotes the hypertrophic scar myofibroblast phenotype by regulating the TGF-beta1 autocrine loop. The Journal of investigative dermatology 68 18401422
2009 The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of endometriosis. Endocrinology 64 19389829
2005 Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo. Journal of cell science 61 15713747
2004 Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling. The Journal of biological chemistry 60 15561701
2015 Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice. Journal of hepatology 58 26334580
2004 A LIM protein, Hic-5, functions as a potential coactivator for Sp1. Journal of cellular biochemistry 56 14755691
2016 Hic-5 is required for myofibroblast differentiation by regulating mechanically dependent MRTF-A nuclear accumulation. Journal of cell science 54 26759173
2012 Paxillin and Hic-5 interaction with vinculin is differentially regulated by Rac1 and RhoA. PloS one 54 22629471
2002 Syndesmos, a syndecan-4 cytoplasmic domain interactor, binds to the focal adhesion adaptor proteins paxillin and Hic-5. The Journal of biological chemistry 53 11805099
2001 Identification and characterization of hic-5/ARA55 as an hsp27 binding protein. The Journal of biological chemistry 50 11546764
2003 Inactivation of androgen receptor coregulator ARA55 inhibits androgen receptor activity and agonist effect of antiandrogens in prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America 48 12700349
2016 Hic-5 remodeling of the stromal matrix promotes breast tumor progression. Oncogene 47 27893716
2008 Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55. Oncogene 47 18762808
2003 Expression of the LIM proteins paxillin and Hic-5 in human tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 47 12642630
2002 Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator. The Journal of biological chemistry 46 11856738
1998 Recruitment of the LIM protein hic-5 to focal contacts of human platelets. Journal of cell science 46 9664039
2006 ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5. The Journal of biological chemistry 44 16624805
2014 Negative regulation of NADPH oxidase 4 by hydrogen peroxide-inducible clone 5 (Hic-5) protein. The Journal of biological chemistry 43 24831009
1998 The LIM domains of hic-5 protein recognize specific DNA fragments in a zinc-dependent manner in vitro. Nucleic acids research 43 9722648
2005 Mechanism of action of Hic-5/androgen receptor activator 55, a LIM domain-containing nuclear receptor coactivator. Molecular endocrinology (Baltimore, Md.) 42 16141357
2014 Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner. Proceedings of the National Academy of Sciences of the United States of America 40 24591583
2005 HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription. The Journal of biological chemistry 39 16291758
2003 Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer. The Prostate 38 12858356
1999 Lepidopteran DALP, and its mammalian ortholog HIC-5, function as negative regulators of muscle differentiation. Proceedings of the National Academy of Sciences of the United States of America 37 10468589
2002 Hic-5 interacts with GIT1 with a different binding mode from paxillin. Journal of biochemistry 36 12153727
2010 Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling. Journal of molecular and cellular cardiology 35 20933520
2006 Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells. Cancer research 34 16849583
2018 Hic-5 regulates fibrillar adhesion formation to control tumor extracellular matrix remodeling through interaction with tensin1. Oncogene 33 29348458
2010 Epithelial Hic-5/ARA55 expression contributes to prostate tumorigenesis and castrate responsiveness. Oncogene 33 20818421
2000 Phosphorylation of Hic-5 at tyrosine 60 by CAKbeta and Fyn. FEBS letters 32 10838081
2014 Hic-5 influences genomic and non-genomic actions of the androgen receptor in prostate myofibroblasts. Molecular and cellular endocrinology 31 24440747
2002 Transcriptional activation of the c-fos gene by a LIM protein, Hic-5. Biochemical and biophysical research communications 31 12445807
2019 HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression. Cell death & disease 30 31740661
2007 Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries. American journal of physiology. Heart and circulatory physiology 30 18083901
2000 Specific decrease in the level of Hic-5, a focal adhesion protein, during immortalization of mouse embryonic fibroblasts, and its association with focal adhesion kinase. Journal of cellular biochemistry 30 10649439
2017 The impact of stromal Hic-5 on the tumorigenesis of colorectal cancer through lysyl oxidase induction and stromal remodeling. Oncogene 29 29242607
2020 Exosome-mediated Hic-5 regulates proliferation and apoptosis of osteosarcoma via Wnt/β-catenin signal pathway. Aging 28 33310972
2007 Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles. The Journal of investigative dermatology 28 17508020
2007 Hic-5 promotes endothelial cell migration to lysophosphatidic acid. American journal of physiology. Heart and circulatory physiology 27 17337598
2005 Involvement of FAK and PTP-PEST in the regulation of redox-sensitive nuclear-cytoplasmic shuttling of a LIM protein, Hic-5. Antioxidants & redox signaling 27 15706082
2001 Involvement of Hic-5 in platelet activation: integrin alphaIIbbeta3-dependent tyrosine phosphorylation and association with proline-rich tyrosine kinase 2. The Biochemical journal 27 11311131
2017 IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. Mucosal immunology 26 28612841
2015 Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells. Investigative ophthalmology & visual science 26 26313302
2007 TGF-beta1 slows the growth of pathogenic myofibroblasts through a mechanism requiring the focal adhesion protein, Hic-5. The Journal of investigative dermatology 24 17671518
2004 Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix targeting and glucocorticoid receptor binding and coactivation. Journal of cellular biochemistry 24 15211577
2018 Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices. Molecular biology of the cell 23 29771639
2013 Inhibition of collagen I accumulation reduces glomerulosclerosis by a Hic-5-dependent mechanism in experimental diabetic nephropathy. Laboratory investigation; a journal of technical methods and pathology 23 23508044
2005 Tyrosine-phosphorylated Hic-5 inhibits epidermal growth factor-induced lamellipodia formation. Experimental cell research 23 16183059
2007 Gonadotropin-releasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5. Neuroendocrinology 22 17202804
2006 Oligomerizing potential of a focal adhesion LIM protein Hic-5 organizing a nuclear-cytoplasmic shuttling complex. The Journal of biological chemistry 21 16737959
2006 Hic-5/ARA55: a prostate stroma-specific AR coactivator. Steroids 21 17166536
2000 Molecular cloning of human Hic-5, a potential regulator involved in signal transduction and cellular senescence. Molecular carcinogenesis 20 10708479
2016 Hic-5 mediates the initiation of endothelial sprouting by regulating a key surface metalloproteinase. Journal of cell science 19 26769900
2015 Hic-5 Mediates TGFβ-Induced Adhesion in Vascular Smooth Muscle Cells by a Nox4-Dependent Mechanism. Arteriosclerosis, thrombosis, and vascular biology 19 25814672
2012 Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target for vascular and other disorders. Journal of atherosclerosis and thrombosis 19 22472216
2011 Hic-5 controls BMP4 responses in prostate cancer cells through interacting with Smads 1, 5 and 8. Oncogene 19 21996749
2009 Upregulation of Hic-5 in glomerulosclerosis and its regulation of mesangial cell apoptosis. Kidney international 19 20010548
2008 Hic-5, an adaptor protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo. Biochemical and biophysical research communications 19 18812162
2014 Identification of Hic-5 as a novel scaffold for the MKK4/p54 JNK pathway in the development of abdominal aortic aneurysms. Journal of the American Heart Association 18 24811612
2012 Cbl-c ubiquitin ligase activity is increased via the interaction of its RING finger domain with a LIM domain of the paxillin homolog, Hic 5. PloS one 18 23145173
2019 The focal adhesion scaffold protein Hic-5 regulates vimentin organization in fibroblasts. Molecular biology of the cell 17 31644368
2014 VDR activity is differentially affected by Hic-5 in prostate cancer and stromal cells. Molecular cancer research : MCR 16 24825850
2008 Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage dependence of cell growth and survival. Molecular biology of the cell 16 18946086
2006 Hic-5, an adaptor-like nuclear receptor coactivator. Nuclear receptor signaling 16 16862225
2012 Hic-5 affects proliferation, migration and invasion of B16 murine melanoma cells. Pigment cell & melanoma research 15 22883018
2011 Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation. The Journal of biological chemistry 15 21515881
2002 Possible involvement of hic-5, a focal adhesion protein, in the differentiation of C2C12 myoblasts. Cell structure and function 15 11937715
1998 Forced expression of hic-5, a senescence-related gene, potentiates a differentiation process of RCT-1 cells induced by retinoic acid. The international journal of biochemistry & cell biology 15 9597752
2019 Hic-5 deficiency protects cerulein-induced chronic pancreatitis via down-regulation of the NF-κB (p65)/IL-6 signalling pathway. Journal of cellular and molecular medicine 14 31797546
2019 PTHR1 May Be Involved in Progression of Osteosarcoma by Regulating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 Axes. DNA and cell biology 13 31536386
2019 Hic-5 in pancreatic stellate cells affects proliferation, apoptosis, migration, invasion of pancreatic cancer cells and postoperative survival time of pancreatic cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 31683179
2017 Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes. The Journal of biological chemistry 13 28381557
2017 Hic-5 regulates epithelial to mesenchymal transition in ovarian cancer cells in a TGFβ1-independent manner. Oncotarget 13 29137281
2015 Role of Hic-5 in the formation of microvilli-like structures and the monocyte-endothelial interaction that accelerates atherosclerosis. Cardiovascular research 12 25587044
2011 HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth. International journal of cell biology 12 22145007
2007 Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis. Experimental cell research 12 17935713
2020 Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis. Scientific reports 11 33154390
2020 Inhibitory Effects of Cypermethrin on Interactions of the Androgen Receptor with Coactivators ARA70 and ARA55. Biomedical and environmental sciences : BES 10 32209174
2019 Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5. Scientific reports 10 31673109
2019 Hic-5 regulates Src-induced invadopodia rosette formation and organization. Molecular biology of the cell 9 30893012
2012 Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice. Journal of thrombosis and haemostasis : JTH 9 22812543
2005 Identification and analysis of Hic-5/ARA55 isoforms: Implications for integrin signaling and steroid hormone action. FEBS letters 9 16219310
2000 Genomic structure and chromosomal mapping of the mouse hic-5 gene that encodes a focal adhesion protein. Gene 9 10831843
2015 Selective coregulator function and restriction of steroid receptor chromatin occupancy by Hic-5. Molecular endocrinology (Baltimore, Md.) 8 25763609