Affinage

FHL1

Four and a half LIM domains protein 1 · UniProt Q13642

Length
323 aa
Mass
36.3 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FHL1 is a multi-isoform LIM-domain scaffold protein, predominantly expressed in striated muscle, that integrates biomechanical and growth-factor signals to control muscle gene expression, fiber differentiation, and stress hypertrophy (PMID:19033658, PMID:23975679). In the cardiomyocyte sarcomere it forms a stretch-sensing complex with the titin N2B domain and MAPK components, acting downstream of Gq to drive pathological left-ventricular hypertrophy in a ventricle-specific manner (PMID:19033658, PMID:31980934); it also assembles into a cytoskeletal complex with PDLIM1, gelsolin, and ACTN1 (PMID:21246116). A central effector function is its binding to and activation of the calcineurin/NFATc1 axis, which promotes skeletal-muscle hypertrophy, oxidative fiber-type switching, and—via an NFATc1–utrophin axis—can reassemble a substitute glycoprotein complex that ameliorates dystrophic pathology (PMID:19075112, PMID:24087791). FHL1 expression is itself a signaling node, induced by Wnt/TCF-LEF and HOXD13 and downstream of Rho/CRIK, while its isoforms localize differentially to focal adhesions, actin filaments, the nucleus, and the nuclear envelope, where FHL1B associates with lamin A/C and emerin and FHL1B/SLIMMER binds the proapoptotic protein Siva-1 and RBP-J to repress Notch/EBNA2-dependent transcription (PMID:10480922, PMID:18760388, PMID:19643733, PMID:27911330, PMID:25676585, PMID:18758158, PMID:16061799). In cancer, FHL1 functions as a Src-regulated tumor suppressor: Src-Cas signaling silences FHL1 via promoter methylation, and Src phosphorylation at Y149/Y272 drives nuclear translocation and BCLAF1 binding, with Kindlin-2 and the deubiquitinase OTUD1 opposing this switch (PMID:16452211, PMID:29434030, PMID:36929488). FHL1 is also an essential host factor for chikungunya and O'nyong-nyong virus replication, binding the nsP3 hypervariable domain through its LIM1 domain (PMID:31554973, PMID:33055253, PMID:37884534). Pathogenic missense mutations in the LIM2/LIM4 domains cause dominant-negative protein aggregation that sequesters wild-type FHL1 and NFATc1, producing reducing body myopathy and related X-linked myopathies (PMID:18274675, PMID:24634512, PMID:20633900).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 1999 High

    Established that FHL1 isoforms occupy distinct subcellular compartments, framing it as a protein whose function is partitioned between focal-adhesion signaling and nuclear-cytoplasmic communication.

    Evidence GFP-fusion live imaging and NLS/NES truncation analysis in COS-7 and myoblast/myotube cells

    PMID:10480922

    Open questions at the time
    • Functional consequences of each localization not defined
    • Did not identify binding partners at focal adhesions or nucleus
  2. 2001 Medium

    Showed isoform-specific nuclear targeting and tissue distribution (FHL1B brain-specific; FHL1C distributed via an RBP-J binding region), connecting FHL1 isoforms to transcriptional machinery.

    Evidence Isoform-specific immunoblot, subcellular fractionation, and tagged-isoform transfection

    PMID:11400158

    Open questions at the time
    • Single lab, antibody-based
    • Functional role of RBP-J interaction not yet tested
  3. 2003 Medium

    Linked FHL1 overexpression to integrin-dependent myocyte morphology, indicating a role in cell-shape and adhesion signaling during differentiation.

    Evidence Overexpression with alpha5beta1-integrin peptide blockade and substrate controls in myocytes

    PMID:12917103

    Open questions at the time
    • Mechanism of integrin engagement unresolved
    • Overexpression-based; endogenous role untested
  4. 2005 Medium

    Placed FHL1 (KyoT1/2) downstream of Rho/CRIK signaling as a suppressor of keratinocyte differentiation, extending its regulatory role beyond muscle.

    Evidence RhoA/CRIK manipulation and KyoT1/2 overexpression with differentiation assays in keratinocytes

    PMID:16061799

    Open questions at the time
    • Direct FHL1 effector targets in keratinocytes unknown
    • Single lab epistasis
  5. 2006 Medium

    Identified FHL1 as a tumor suppressor whose silencing by promoter methylation is required for Src-driven transformation, defining the Src-Cas-FHL1 axis.

    Evidence Genome-wide expression analysis with Src/Cas manipulation and transformation assays in tumor cells

    PMID:16452211

    Open questions at the time
    • Downstream tumor-suppressive effectors of FHL1 not identified here
    • Correlative methylation link
  6. 2008 High

    Established FHL1 as a cardiac biomechanical stress sensor acting downstream of Gq, by tying it to titin N2B and MAPK signaling in hypertrophy.

    Evidence Fhl1 knockout mice with TAC, Gq transgenic epistasis, and Co-IP with titin N2B/MAPK components

    PMID:19033658

    Open questions at the time
    • Precise stretch-to-MAPK transduction step undefined
    • Stoichiometry of the sarcomeric complex unknown
  7. 2008 High

    Identified FHL1 as the gene mutated in reducing body myopathy and showed mutants form dominant-negative aggregates, defining a gain-of-toxicity disease mechanism.

    Evidence Laser microdissection proteomics of inclusions plus mutant FHL1 transfection in COS-7/C2C12 cells

    PMID:18274675

    Open questions at the time
    • Why specific LIM mutations aggregate not yet defined
    • Spectrum of trapped proteins incomplete
  8. 2008 Medium

    Refined the tumor-suppressor mechanism by showing Src promotes FHL1 promoter methylation independently of MAPK and that FHL1 induces Sdpr in tumors.

    Evidence Bisulfite sequencing, MAPK inhibitor epistasis, and tumor expression arrays/IHC

    PMID:18422756

    Open questions at the time
    • Direct enzymatic link from Src/Cas to DNA methylation not shown
    • Sdpr functional contribution untested
  9. 2008 Medium

    Identified Talin1 as an FHL1 partner in pulmonary artery smooth muscle and tied FHL1 to migration/proliferation in pulmonary hypertension.

    Evidence Proteomics, siRNA/overexpression, and Co-IP with Talin1 in primary human PASMCs

    PMID:18725486

    Open questions at the time
    • Functional requirement of the Talin1 interaction not dissected
    • Single disease context
  10. 2008 Medium

    Showed KyoT3/FHL1 represses RBP-J-dependent transactivation, linking an FHL1 isoform to Notch/EBNA2 transcriptional control.

    Evidence EGFP localization, Co-IP with RBP-J, and luciferase reporter assays

    PMID:18760388

    Open questions at the time
    • Physiological context of Notch repression unclear
    • Reporter-based functional readout
  11. 2008 Medium

    Demonstrated that HOXD13 directly binds the FHL1 promoter in developing limb, placing FHL1 in a developmental transcriptional program.

    Evidence Luciferase, EMSA, and ChIP from developing rat limb

    PMID:18758158

    Open questions at the time
    • Functional consequence of FHL1 in limb development not tested
    • Single developmental system
  12. 2009 High

    Showed SLIMMER/FHL1B binds the proapoptotic Siva-1 and delays apoptosis, assigning an isoform-specific survival function with dynamic localization across differentiation.

    Evidence Yeast two-hybrid, direct binding, GST pulldown from muscle, co-localization, and apoptosis assay in C2C12

    PMID:19643733

    Open questions at the time
    • Mechanism by which FHL1B blocks Siva-1 apoptosis undefined
    • In vivo relevance untested
  13. 2009 Medium

    Identified RIP140 as an FHL1 partner enhancing repression of estrogen-responsive transcription, extending FHL1 into nuclear-receptor corepression.

    Evidence Yeast two-hybrid, Co-IP, reporter assays, and siRNA in mammalian cells

    PMID:19401155

    Open questions at the time
    • Whether all FHL1 LIM domains directly contact RIP140 not structurally resolved
    • Single lab
  14. 2010 High

    Established the FHL1-NFATc1 axis as the core effector for skeletal muscle hypertrophy and showed disease mutants sequester NFATc1, unifying hypertrophic and myopathic mechanisms.

    Evidence Reciprocal Co-IP, calcineurin-inhibitor rescue in C2C12, NFATc1 localization, and FHL1 transgenic mice

    PMID:19075112

    Open questions at the time
    • Direct biochemical step by which FHL1 potentiates NFATc1 unclear
    • Other calcineurin pathway nodes untested
  15. 2011 Medium

    Defined FHL1 binding to the ER AF-1 domain and repression of estrogen-responsive promoters, broadening its corepressor role to estrogen receptor signaling.

    Evidence Co-IP, ChIP, reporter assays, and siRNA knockdown in breast cancer cells

    PMID:19840196

    Open questions at the time
    • Relationship to FHL1-RIP140 corepression not integrated
    • Single lab
  16. 2011 Medium

    Defined a native FHL1 cytoskeletal complex (PDLIM1, gelsolin, ACTN1) in heart, supporting its scaffold function at the sarcomere.

    Evidence Tandem affinity purification-MS in HEK-293, reciprocal Co-IP in mouse heart, and 3D microscopy

    PMID:21246116

    Open questions at the time
    • Functional role of each complex member with FHL1 not dissected
    • Stoichiometry unknown
  17. 2013 High

    Demonstrated FHL1A is required in vivo for muscle fiber differentiation/maturation and that loss causes age-dependent myopathy with autophagy upregulation.

    Evidence FHL1-null mice with histology/EM/function and isoform-specific FHL1A rescue in primary myoblasts

    PMID:23975679

    Open questions at the time
    • Mechanism linking FHL1 loss to autophagy increase undefined here
    • Isoform-specific contributions only partially separated
  18. 2013 High

    Extended the FHL1-NFATc1 axis to drive utrophin expression and rescue dystrophic muscle, establishing a therapeutically relevant FHL1-NFATc1-utrophin pathway.

    Evidence FHL1 transgenic/mdx double-mutant mice, utrophin promoter reporter, and membrane stability/function assays

    PMID:24087791

    Open questions at the time
    • Durability and translatability of utrophin induction not addressed
    • Direct NFATc1-utrophin promoter occupancy not fully mapped
  19. 2014 Medium

    Showed disease mutants segregate by phenotype—aggregation (RBM/SPM/XMPMA) versus reduced expression (HCM/EDMD)—and confirmed FHL1 acts through NFATc1 in differentiation via rescue.

    Evidence Disease-mutant expression in C2C12, Menadione-NBT staining, and constitutively active NFATc1 rescue

    PMID:24634512

    Open questions at the time
    • Why mutation class dictates aggregation vs degradation unclear
    • Cell-line based
  20. 2014 Medium

    Revealed that cardiac stress reprograms Fhl1 transcriptional start-site usage to produce a protective stress isoform, redefining FHL1 as an adaptive HCM response.

    Evidence 5'RNA-Seq, Fhl1 ablation in HCM mice, isoform detection, and human cardiomyopathy samples

    PMID:24509080

    Open questions at the time
    • Function of the stress-specific isoform not biochemically defined
    • Reconciliation with FHL1's pro-hypertrophic role needed
  21. 2015 Medium

    Showed FHL1 potentiates myostatin/TGFβ-SMAD signaling to promote muscle atrophy, revealing a context-dependent atrophic function opposing its hypertrophic role.

    Evidence SMAD reporter, myotube wasting, and in vivo FHL1/myostatin co-electroporation

    PMID:26504741

    Open questions at the time
    • Molecular step by which FHL1 amplifies SMAD signaling unknown
    • Reconciliation with pro-hypertrophic NFATc1 role unresolved
  22. 2015 Medium

    Identified FHL1 as a granzyme B substrate and autoantigen in inflammatory myopathy, linking FHL1 fragmentation to muscle autoimmunity.

    Evidence Granzyme B cleavage assay, anti-FHL1 autoantibody ELISA in patients, and myositis-prone mouse immunization

    PMID:26551678

    Open questions at the time
    • Causal chain from cleavage to autoantibody generation incomplete
    • Single lab patient cohort
  23. 2015 Medium

    Established FHL1 as a Wnt/TCF-LEF transcriptional target required for myotube formation, identifying an upstream regulator of FHL1 in myogenesis.

    Evidence Fhl1 promoter reporter, TCF/LEF site mutagenesis, β-catenin/LiCl treatment, and siRNA in C2C12

    PMID:25676585

    Open questions at the time
    • In vivo Wnt-FHL1 dependence not tested
    • Other myogenic inputs not compared
  24. 2016 Medium

    Localized FHL1B to the nuclear envelope with lamin A/C and emerin and showed its dysregulation in EDMD patient myoblasts, connecting an FHL1 isoform to nuclear-envelope myopathy.

    Evidence Immunofluorescence, western blot, and fractionation in primary human and EDMD-patient myoblasts

    PMID:27911330

    Open questions at the time
    • Functional role of FHL1B at the nuclear envelope unresolved
    • Whether FHL1B elevation is compensatory or pathogenic unclear
  25. 2018 High

    Defined the phosphorylation switch converting FHL1 from cytoplasmic tumor suppressor to nuclear oncogenic factor, with Kindlin-2 antagonizing Src at focal adhesions.

    Evidence Src kinase assay, Y149/Y272 mutagenesis, Co-IP with BCLAF1 and Kindlin-2, fractionation, and proliferation assays

    PMID:29434030

    Open questions at the time
    • BCLAF1 target genes driving growth not identified
    • Tissue contexts where switch operates limited
  26. 2019 Medium

    Linked FHL1 to LC3 and autophagosome formation in myoblast differentiation and anti-atrophy regulation, integrating FHL1 into autophagy control.

    Evidence FHL1-LC3 Co-IP/co-IF and siRNA/overexpression with autophagy/atrophy marker readouts in chicken myoblasts

    PMID:31637727

    Open questions at the time
    • Whether FHL1-LC3 binding is direct unproven
    • Cross-species generalization to mammalian muscle untested
  27. 2019 High

    Identified FHL1 as an essential host factor for CHIKV replication through direct binding of the nsP3 hypervariable domain, establishing a proviral function.

    Evidence FHL1 KO/knockdown cells, direct binding, replication assays, re-expression rescue, and Fhl1-KO mice

    PMID:31554973

    Open questions at the time
    • Mechanistic role of FHL1 in replication complex assembly undefined here
    • Which LIM domain mediates binding not yet resolved
  28. 2020 High

    Mapped the FHL1-nsP3 interaction to the LIM1 domain at a site overlapping CD2AP, providing structural resolution of the proviral interface.

    Evidence NMR structural mapping, LIM truncation analysis, and CHIKV replication/competition assays

    PMID:33055253

    Open questions at the time
    • Whether host LIM1 function is hijacked or merely scaffolds nsP3 unclear
    • Single lab
  29. 2020 Medium

    Showed FHL1-mediated hypertrophic signaling is ventricle-specific, required for LV but dispensable for RV pressure-overload hypertrophy.

    Evidence FHL1-/- mice with pulmonary arterial banding versus aortic constriction and echocardiography

    PMID:31980934

    Open questions at the time
    • Basis for ventricle-specific dependence unknown
    • Compensating factors in RV not identified
  30. 2022 Medium

    Revealed a post-translational FHL1 mechanism promoting blastocyst-epithelial adhesion via HOXA10 stabilization through SIRT2-mediated deacetylation and downstream integrin/FAK activation.

    Evidence FHL1 overexpression/knockdown, mouse uterine knockdown, HOXA10-SIRT2 Co-IP, stability assays, and SIRT2 inhibitors

    PMID:36418297

    Open questions at the time
    • How FHL1 enhances HOXA10-SIRT2 binding not biochemically defined
    • Single reproductive context
  31. 2023 High

    Demonstrated virus-specific requirement for FHL1 in vivo (CHIKV/ONNV but not RRV/MAYV) and that a non-binding viral mutant is avirulent, validating FHL1 as a therapeutic and vaccine target.

    Evidence FHL1-/- mice infected with multiple alphaviruses, nsP3 pull-downs, and engineered CHIKV-ΔFHL1 challenge studies

    PMID:37884534

    Open questions at the time
    • Why some alphavirus nsP3 fail to bind FHL1 unresolved
    • Host signaling consequences of FHL1 hijacking unknown
  32. 2023 Medium

    Identified OTUD1 as a deubiquitinase that stabilizes FHL1 to restrain lung adenocarcinoma, adding post-translational control to FHL1's tumor-suppressor regulation.

    Evidence IP-MS, Co-IP, protein-level assays with OTUD1 manipulation, and in vitro/in vivo tumor growth

    PMID:36929488

    Open questions at the time
    • The opposing E3 ligase ubiquitinating FHL1 not identified
    • Integration with Src-driven FHL1 silencing unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single LIM-domain scaffold reconciles opposing roles—pro-hypertrophic NFATc1 activation versus pro-atrophic myostatin amplification, tumor suppression versus phospho-driven oncogenesis—through isoform identity, post-translational modification, and partner selection remains unresolved.
  • No unified model linking isoform/PTM state to functional output
  • Structural basis of LIM-domain partner discrimination undefined
  • Direct enzymatic activity, if any, of FHL1 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 5 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-397014 Muscle contraction 3
Partners
BCLAF1FERMT2NFATC1PDLIM1RBPJSIVA1TLN1TTN
Complex memberships
FHL1-PDLIM1-gelsolin-ACTN1 cytoskeletal complexFHL1-titin N2B sarcomeric stretch-sensor complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 FHL1 forms a complex within the cardiomyocyte sarcomere that senses biomechanical stress via the N2B stretch sensor domain of titin and initiates changes in titin- and MAPK-mediated responses important for sarcomere extensibility and intracellular signaling. Fhl1-deficient mice show blunted hypertrophic response to pressure overload, and Fhl1 deficiency prevents cardiomyopathy in Gq transgenic mice, placing FHL1 downstream of Gq signaling in pathological hypertrophy. Fhl1 knockout mice + transverse aortic constriction, Gq transgenic mouse epistasis, co-immunoprecipitation with titin N2B domain and MAPK components The Journal of clinical investigation High 19033658
2010 FHL1 binds to the calcineurin-regulated transcription factor NFATc1, enhancing NFATc1 transcriptional activity. FHL1 overexpression promotes skeletal muscle hypertrophy and an oxidative fiber-type switch via this calcineurin/NFATc1 signaling axis; RBM-mutant FHL1 sequesters NFATc1 in aggregates, reducing NFAT nuclear translocation and transcriptional activity. Co-immunoprecipitation of FHL1 with NFATc1; calcineurin inhibitor rescue of FHL1-induced hypertrophic myotube phenotype in C2C12 cells; NFATc1 localization studies; FHL1 transgenic mice The Journal of cell biology High 19075112
1999 SLIM1 (FHL1) localizes to focal adhesions and actin filaments in COS-7 cells. The isoform SLIMMER (FHL1B/KyoT3) localizes to the nucleus of myoblasts via a bipartite nuclear localization signal and is exported to the cytoplasm of myotubes via a leucine-rich nuclear export sequence. These distinct localizations suggest separate roles in focal adhesion signaling versus nuclear-cytoplasmic communication. GFP fusion protein live-cell imaging in COS-7 cells and Sol8 myoblasts/myotubes; truncation mutant analysis of NLS and NES sequences; immunofluorescence The Journal of biological chemistry High 10480922
2003 SLIM1/FHL1 overexpression in differentiating skeletal myocytes induces alpha5beta1-integrin-dependent hyperelongation; in undifferentiated reserve cells it induces integrin-mediated cytoplasmic branching. These effects were blocked by poly-L-lysine plating or peptide blockade of alpha5beta1-integrin ligand binding, establishing a specific dependence on alpha5beta1-integrin signaling. SLIM1 overexpression in Sol8/C2C12 cells; peptide blockade of alpha5beta1-integrin; poly-L-lysine substrate control; cell morphology analysis American journal of physiology. Cell physiology Medium 12917103
2008 FHL1 is identified as the protein mutated in reducing body myopathy (RBM). Mutant FHL1 expressed in COS-7 and C2C12 cells forms aggresome-like inclusions that incorporate both mutant and wild-type FHL1 and trap other proteins in a dominant-negative manner. Laser microdissection of inclusions + nanoflow LC-MS/MS proteomics; transfection of mutant FHL1 into COS-7 and C2C12 cells; immunofluorescence imaging of aggregates The Journal of clinical investigation High 18274675
2009 FHL1 interacts directly with the hypervariable domain (HVD) of chikungunya virus nsP3 protein, and this interaction is essential for CHIKV RNA replication. Cells lacking FHL1 are resistant to CHIKV infection; FHL1 expression in non-expressing cells promotes CHIKV infection. FHL1 knockout/knockdown cells, direct binding assay, viral RNA replication assay, FHL1 expression rescue in non-expressing cells, Fhl1-knockout mice infected with CHIKV Nature High 31554973
2020 NMR structural studies revealed that FHL1 binds CHIKV nsP3 HVD predominantly via its LIM1 domain, with the binding site overlapping that of CD2AP. FHL1 and CD2AP have additive proviral effects on CHIKV replication efficiency. NMR-based structural mapping of FHL1-HVD interaction; LIM domain truncation analysis; CHIKV replication assays in FHL1 KO cell lines; competition with CD2AP Journal of virology High 33055253
2001 FHL1C (KyoT2 homolog) localizes to both nucleus and cytoplasm; its C-terminal RBP-J binding region is required for this distribution. FHL1B localizes predominantly to the nucleus via its C-terminal bipartite NLS and is brain-specifically expressed. Immunoblot with isoform-specific antibodies; subcellular fractionation; transfection of tagged isoforms; RT-PCR tissue distribution Journal of cellular biochemistry Medium 11400158
2008 KyoT3 (FHL1 isoform) localizes preferentially to the nucleus, interacts with RBP-J via co-immunoprecipitation, and represses RBP-J-dependent transactivation activated by both Notch intracellular domain and EBV nuclear antigen 2. EGFP fusion protein localization; co-immunoprecipitation of KyoT3 with RBP-J; luciferase reporter assay for RBP-J-dependent promoter Biochimica et biophysica acta Medium 18760388
2006 Src phosphorylates Cas to suppress FHL1 expression (via promoter methylation), and suppression of FHL1 is required for Src to promote tumor cell anchorage-independent growth and migration, placing FHL1 downstream of the Src-Cas signaling axis as a tumor suppressor. Gene expression analysis of >14,000 genes; Src and Cas expression/inhibition experiments; anchorage-independent growth and migration assays in tumor cells normalized by non-transformed cell contact Cancer research Medium 16452211
2008 Src promotes FHL1 promoter methylation (via Cas) to suppress FHL1 expression independently of MAPK activity. FHL1 in turn induces Sdpr expression in Src-transformed cells. FHL1 and Sdpr are coordinately suppressed in breast, kidney, and prostate tumors. DNA bisulfite modification and sequencing; MAPK inhibitor treatment; gene expression arrays; immunohistochemistry of tumor vs. normal tissue Cancer science Medium 18422756
2018 Src phosphorylates FHL1 at Y149 and Y272, causing phosphorylated FHL1 to translocate to the nucleus where it binds the transcription factor BCLAF1 and promotes tumor cell growth. Kindlin-2 interacts with FHL1 at focal adhesions and competes with Src for FHL1 binding, suppressing Src-mediated FHL1 phosphorylation. In vitro Src kinase assay; site-directed mutagenesis of Y149 and Y272; co-immunoprecipitation of FHL1 with BCLAF1 and Kindlin-2; subcellular fractionation; tumor cell proliferation assays The Journal of cell biology High 29434030
2011 FHL1 physically interacts with estrogen receptors (ERs), specifically binding the activation function-1 (AF-1) domain of ER. This interaction is required for FHL1 repression of estrogen-responsive gene transcription; FHL1 affects ER recruitment to estrogen-responsive promoters. Co-immunoprecipitation; chromatin immunoprecipitation (ChIP); luciferase reporter assays; FHL1 siRNA knockdown; overexpression in breast cancer cells Journal of cellular and molecular medicine Medium 19840196
2009 FHL1 interacts with RIP140 (receptor interacting protein of 140 kDa) in vitro and in mammalian cells; estrogen enhances this interaction. All domains of FHL1 are required for RIP140 binding. FHL1 enhances RIP140 repression of estrogen signaling and synergistically inhibits transcription of the estrogen-responsive gene pS2. Yeast two-hybrid screening; co-immunoprecipitation in mammalian cells; luciferase reporter assay; FHL1 siRNA knockdown; FHL1 domain deletion mutants The international journal of biochemistry & cell biology Medium 19401155
2011 FHL1 exists as part of a protein complex that includes PDLIM1, gelsolin (GSN), and ACTN1 (alpha-actinin 1), as identified by tandem affinity purification from HEK-293 cells confirmed by immunoprecipitation from mouse heart ventricles and 3D fluorescence microscopy in adult cardiomyocytes. Tandem affinity purification from HEK-293 cells; LC-MS identification of interactors; reciprocal immunoprecipitation from mouse heart ventricles; 3D fluorescence microscopy Molecular bioSystems Medium 21246116
2013 Loss of FHL1 in mice leads to an age-dependent skeletal muscle myopathy with myofibrillar and intermyofibrillar disorganization, impaired oxidative capacity, and increased autophagic activity. Re-expression of the FHL1A isoform specifically rescues early muscle fiber differentiation and maturation defects in primary FHL1-null myoblasts, establishing FHL1A as necessary for proper muscle fiber differentiation. FHL1-null mice; histological, ultrastructural (EM), and functional muscle analyses; primary myoblast isolation and re-expression of FHL1A isoform; longitudinal survival study Human molecular genetics High 23975679
2005 Rho/CRIK signaling suppresses keratinocyte differentiation through up-regulation of KyoT1/2 (FHL1) expression. Elevated KyoT1/2 expression suppresses differentiation similarly to activated Rho and CRIK, placing FHL1 downstream of the Rho-CRIK pathway in keratinocyte self-renewal/differentiation control. RhoA and CRIK overexpression/inhibition in keratinocytes; gene expression analysis; KyoT1/2 overexpression in keratinocytes with differentiation assays Proceedings of the National Academy of Sciences of the United States of America Medium 16061799
2015 FHL1 activates myostatin signaling; FHL1 increases myostatin activity on a SMAD reporter and increases myostatin-dependent myotube wasting. Co-expression of FHL1 and myostatin in mice reduced fiber diameter to a greater extent than myostatin alone, demonstrating that FHL1 can promote muscle atrophy by potentiating TGFβ/myostatin-SMAD signaling. SMAD luciferase reporter assay; myotube wasting assay; in vivo electroporation of FHL1 and myostatin into mouse muscle; fiber diameter measurement FEBS open bio Medium 26504741
2009 SLIMMER (FHL1B/KyoT3) interacts with the proapoptotic protein Siva-1 via yeast two-hybrid, direct binding, and GST pulldown from skeletal muscle lysates. SLIMMER and Siva-1 co-localize in the nucleus of C2C12 myoblasts and redistribute to the cytoplasm upon differentiation, and to the Z-line in mature skeletal muscle. SLIMMER delays Siva-1-dependent apoptosis in C2C12 myoblasts. Yeast two-hybrid screen; direct binding assay; GST pulldown from muscle lysates; co-localization by immunofluorescence; apoptosis assay in C2C12 myoblasts The Journal of biological chemistry High 19643733
2013 FHL1 overexpression promotes NFATc1 activation of the utrophin promoter and increases sarcolemmal expression of utrophin in mdx mice, directing assembly of a substitute utrophin-glycoprotein complex, thereby ameliorating dystrophic pathology. This defines a novel FHL1-NFATc1-utrophin signaling axis. FHL1 transgenic/mdx double-mutant mice; utrophin promoter-luciferase reporter assay; sarcolemmal membrane stability assays; immunohistochemistry; muscle function tests Human molecular genetics High 24087791
2008 FHL1 expression in pulmonary artery smooth muscle cells is upregulated in pulmonary hypertension. FHL1 knockdown suppresses, while FHL1 overexpression increases, PASMC migration and proliferation. Co-immunoprecipitation identified Talin1 as a new FHL1-interacting partner in this context. 2D-PAGE proteomics; siRNA knockdown; adenoviral overexpression; co-immunoprecipitation with Talin1; migration and proliferation assays in primary human PASMCs Circulation Medium 18725486
2008 RBM and SPM FHL1 mutations affecting conserved zinc-coordinating residues in the LIM2 domain lead to protein aggregation. Molecular dynamics simulations of LIM2 mutations showed increased nonpolar solvent-accessible surface area without major structural distortion or disruption of zinc binding, suggesting the mutations increase propensity to aggregate. Transfection of mutant FHL1 into C2C12 cells (aggregate formation); molecular dynamics simulations of LIM2 domain mutations; immunohistochemistry of muscle biopsies Journal of the neurological sciences Medium 20633900
2014 RBM, SPM, and XMPMA FHL1 mutants expressed in C2C12 cells form aggregates positive for the reducing body stain Menadione-NBT and impair myoblast differentiation. HCM and EDMD FHL1 mutants generally show reduced protein expression instead of aggregation. SPM and XMPMA mutant-induced impaired myotube formation is partially rescued by constitutively active NFATc1, confirming FHL1 acts through NFATc1 signaling in myoblast differentiation. Expression of disease mutants in C2C12 cells; Menadione-NBT staining; myotube formation assay; constitutively active NFATc1 rescue experiment; immunofluorescence Journal of cell science Medium 24634512
2016 FHL1B isoform localizes to the nuclear envelope of primary human myoblasts, co-localizing with but independently of lamin A/C and emerin. FHL1B protein expression is markedly reduced during myoblast differentiation. FHL1B is elevated in myoblasts from FHL1-related EDMD patients (where the mutation only affects FHL1A) and from LMNA-related EDMD patients. Immunofluorescence of primary human myoblasts; western blotting; subcellular fractionation; analysis of EDMD patient myoblasts Journal of neuromuscular diseases Medium 27911330
2019 FHL1 regulates myoblast differentiation through interaction with LC3; FHL1 and LC3 interact by immunoprecipitation and co-immunofluorescence to regulate autophagosome formation. FHL1 silencing inhibits ATG5 and ATG7 expression, promotes apoptosis (increased cleaved caspase-3 and PARP), and FHL1 rescues skeletal muscle atrophy by regulating Atrogin-1 and MuRF1 expression. FHL1 siRNA knockdown and overexpression in chicken myoblasts; immunoprecipitation of FHL1 with LC3; immunofluorescence co-localization; western blot for autophagy and differentiation markers Journal of cellular physiology Medium 31637727
2022 FHL1 promotes blastocyst-epithelial adhesion by increasing HOXA10 protein stability and activating HOXA10 transcriptional activity via enhanced deacetylation of HOXA10 through increased HOXA10-SIRT2 binding. FHL1 does not regulate HOXA10 mRNA but acts post-translationally; SIRT2-specific inhibitors block this effect. FHL1 also activates the downstream β3 integrin/FAK pathway. FHL1 overexpression/knockdown in endometrial epithelial cells; mouse uterine FHL1 knockdown inhibiting embryo implantation; co-immunoprecipitation of HOXA10-SIRT2; HOXA10 protein stability assays; SIRT2 inhibitor treatment; β3 integrin/FAK pathway analysis Cell death discovery Medium 36418297
2015 FHL1 expression is induced by Wnt signaling (β-catenin or LiCl) through TCF/LEF binding sites in the Fhl1 promoter; mutation of two TCF/LEF consensus sites significantly decreases promoter activity. Fhl1 knockdown in C2C12 cells reduces myotube formation, establishing Fhl1 as a downstream effector of Wnt signaling in myogenesis. Fhl1 promoter-luciferase reporter assay; TCF/LEF site mutagenesis; β-catenin and LiCl treatment; Fhl1 siRNA knockdown; myotube formation assay in C2C12 cells Journal of cellular biochemistry Medium 25676585
2023 FHL1 is required for CHIKV and ONNV (but not RRV or MAYV) pathogenesis in vivo; FHL1-/- mice infected with CHIKV or ONNV show reduced arthritis, myositis, and immune infiltrates. Pull-down assays confirmed CHIKV and ONNV nsP3 interact with FHL1 while RRV and MAYV nsP3 do not. A CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1) was avirulent and conferred protection against subsequent CHIKV/ONNV challenge. FHL1-/- mouse generation; in vivo infection with multiple alphaviruses; pull-down assays of nsP3 with FHL1; engineering of CHIKV-ΔFHL1 mutant; challenge experiments Nature communications High 37884534
2023 The deubiquitinase OTUD1 deubiquitinates and stabilizes FHL1 protein, inhibiting lung adenocarcinoma progression. OTUD1 was identified as a FHL1-interacting protein by IP-MS, and co-IP confirmed their interaction; OTUD1 overexpression increased FHL1 protein levels without affecting FHL1 transcription. IP-MS identification of OTUD1 as FHL1 interactor; co-immunoprecipitation; western blot for FHL1 protein levels with OTUD1 manipulation; in vitro and in vivo tumor growth assays Cellular oncology (Dordrecht, Netherlands) Medium 36929488
2008 HOXD13 directly regulates FHL1 expression in rat embryo limb development. Luciferase assay and EMSA identified a novel FHL1 promoter region that directly interacts with HOXD13. Chromatin immunoprecipitation confirmed that endogenous HOXD13 interacts with this FHL1 promoter region in the developing limb. Luciferase reporter assay; EMSA; ChIP from developing rat limb; immunofluorescence staining of embryonic tissue Cytogenetic and genome research Medium 18758158
2015 FHL1 is a target of the cytotoxic protease granzyme B, indicating that generation of FHL1 fragments may initiate FHL1 autoimmunity in inflammatory myopathies (IIM). Anti-FHL1 autoantibodies were detected in 25% of IIM patients and were predictive for muscle atrophy and vasculitis. Granzyme B cleavage assay of FHL1; ELISA detection of anti-FHL1 autoantibodies in patient serum; immunization of myositis-prone mice with FHL1 The Journal of clinical investigation Medium 26551678
2014 5'RNA-Seq revealed that HCM induces altered transcriptional start-site usage of Fhl1, producing a distinct protein isoform in stressed myocytes. Genetic ablation of Fhl1 in HCM mice was deleterious, demonstrating that the stress-induced Fhl1 transcriptional change is salutary. This conserved response was also found in humans with genetic or acquired cardiomyopathies. 5'RNA-Seq for genome-wide start-site usage; Fhl1 genetic ablation in HCM mouse model; isoform-specific protein detection; analysis of human HCM samples The Journal of clinical investigation Medium 24509080
2020 FHL1-/- mice subjected to left ventricular pressure overload showed a blunted hypertrophic response (confirming the published role of FHL1 in LV hypertrophy), but the same FHL1 deficiency did not diminish right ventricular hypertrophy, hypertrophic signaling, or dysfunction following pulmonary arterial banding, demonstrating that FHL1-mediated hypertrophic signaling is ventricle-specific. FHL1-/- mice; pulmonary arterial banding for RV pressure overload; echocardiography; gene expression analysis; comparison with transverse aortic constriction LV model Basic research in cardiology Medium 31980934

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. The Journal of clinical investigation 203 19033658
2003 Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins. The Journal of biological chemistry 183 14607842
2000 Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation 179 11120693
2009 Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. American journal of human genetics 177 19716112
2007 Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration. Molecular immunology 155 17399790
2008 Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy. The Journal of clinical investigation 131 18274675
2006 Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1. Molecular microbiology 128 16925556
2008 An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1. American journal of human genetics 126 18179888
2012 Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. The Journal of infectious diseases 120 22291192
2008 Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. The Journal of cell biology 113 19075112
2002 The yeast Candida albicans binds complement regulators factor H and FHL-1. Infection and immunity 108 12183569
2007 Gpm1p is a factor H-, FHL-1-, and plasminogen-binding surface protein of Candida albicans. The Journal of biological chemistry 106 17959597
2012 Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. Human molecular genetics 101 22523091
2009 Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein. Molecular immunology 91 19850343
1999 Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication. The Journal of biological chemistry 91 10480922
1998 Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1). Gene 85 9714789
1994 Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a fork head protein involved in rRNA processing. Molecular and cellular biology 84 8164651
2002 Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells. British journal of cancer 79 12402151
2009 Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1. Brain : a journal of neurology 78 19181672
2019 FHL1 is a major host factor for chikungunya virus infection. Nature 74 31554973
1999 The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. Biochemical and biophysical research communications 74 10049693
2008 Fhl-1, a new key protein in pulmonary hypertension. Circulation 72 18725486
2008 Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate. Cancer science 71 18422756
2011 Downregulation and growth inhibitory role of FHL1 in lung cancer. International journal of cancer 65 21702045
2009 Consequences of mutations within the C terminus of the FHL1 gene. Neurology 61 19687455
2014 5'RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy. The Journal of clinical investigation 55 24509080
2008 Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1). Neuromuscular disorders : NMD 53 18952429
2006 SRC uses Cas to suppress Fhl1 in order to promote nonanchored growth and migration of tumor cells. Cancer research 52 16452211
2014 MiR-410 is overexpressed in liver and colorectal tumors and enhances tumor cell growth by silencing FHL1 via a direct/indirect mechanism. PloS one 50 25272045
2010 Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation. Annals of neurology 50 20186852
2003 Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces alpha 5 beta 1-integrin-dependent myocyte elongation. American journal of physiology. Cell physiology 50 12917103
2011 Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy. Neurology 48 22094483
2011 FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth. Journal of cellular and molecular medicine 46 19840196
2001 Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1). Journal of cellular biochemistry 45 11400158
2013 Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice. Human molecular genetics 43 23975679
2012 FHL1 on chromosome X is a single-hit gastrointestinal tumor-suppressor gene and contributes to the formation of an epigenetic field defect. Oncogene 42 22689052
2019 Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen. Frontiers in immunology 41 31824478
2010 A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations. Journal of the neurological sciences 39 20633900
2000 The LIM-domain protein FHL1 (SLIM 1) exhibits functional regulation in skeletal muscle. Molecular cell biology research communications : MCBRC 38 10860860
2015 Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. The Journal of clinical investigation 37 26551678
2013 Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders. Journal of neuropathology and experimental neurology 36 23965743
1999 Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1. Gene 36 10352231
1999 Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1. Gene 36 10524257
2008 Clinical significance of loss of Fhl1 expression in human gastric cancer. Annals of surgical oncology 34 18465173
2010 Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1. Neuropediatrics 33 20571991
2009 Four and a half LIM domains 1 (FHL1) and receptor interacting protein of 140kDa (RIP140) interact and cooperate in estrogen signaling. The international journal of biochemistry & cell biology 33 19401155
2003 Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis. Clinical and experimental immunology 33 12780697
2019 Self versus Nonself Discrimination by the Soluble Complement Regulators Factor H and FHL-1. Journal of immunology (Baltimore, Md. : 1950) 32 30745459
2006 Binding of human complement regulators FHL-1 and factor H to CRASP-1 orthologs of Borrelia burgdorferi. Wiener klinische Wochenschrift 32 17160605
2011 Expression of FHL1 in gastric cancer tissue and its correlation with the invasion and metastasis of gastric cancer. Molecular and cellular biochemistry 31 22143536
2006 Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation. Biochimica et biophysica acta 31 17174532
2019 Overexpression Of hsa-miR-664a-3p Is Associated With Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Via Targeting FHL1. International journal of chronic obstructive pulmonary disease 27 31632001
2011 Identification of an FHL1 protein complex containing ACTN1, ACTN4, and PDLIM1 using affinity purifications and MS-based protein-protein interaction analysis. Molecular bioSystems 27 21246116
2005 Negative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression. Proceedings of the National Academy of Sciences of the United States of America 27 16061799
2018 Src-mediated phosphorylation converts FHL1 from tumor suppressor to tumor promoter. The Journal of cell biology 26 29434030
2015 FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy. FEBS open bio 26 26504741
2013 Proteomic characterization of aggregate components in an intrafamilial variable FHL1-associated myopathy. Neuromuscular disorders : NMD 26 23489660
2011 Reducing body myopathy and other FHL1-related muscular disorders. Seminars in pediatric neurology 26 22172421
2012 Novel FHL1 mutation in a family with reducing body myopathy. Muscle & nerve 25 23169582
2019 FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3. Journal of cellular physiology 24 31637727
2014 Structural characterization of CspZ, a complement regulator factor H and FHL-1 binding protein from Borrelia burgdorferi. The FEBS journal 24 24702793
1999 The cardiac expression of striated muscle LIM protein 1 (SLIM1) is restricted to the outflow tract of the developing heart. Journal of molecular and cellular cardiology 24 10329211
2016 Exome sequencing identifies variants in two genes encoding the LIM-proteins NRAP and FHL1 in an Italian patient with BAG3 myofibrillar myopathy. Journal of muscle research and cell motility 23 27443559
2014 FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation. Journal of cell science 23 24634512
2009 Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H. International journal of medical microbiology : IJMM 23 19138559
2008 KyoT3, an isoform of murine FHL1, associates with the transcription factor RBP-J and represses the RBP-J-mediated transactivation. Biochimica et biophysica acta 23 18760388
2019 Long Intergenic Noncoding RNA 00261 Acts as a Tumor Suppressor in Non-Small Cell Lung Cancer via Regulating miR-105/FHL1 Axis. Journal of Cancer 22 31772674
2017 Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer. Oncology letters 21 29113254
2015 Estrogen enhances activity of Wnt signaling during osteogenesis by inducing Fhl1 expression. Journal of cellular biochemistry 21 25676585
2008 HOXD13 may play a role in idiopathic congenital clubfoot by regulating the expression of FHL1. Cytogenetic and genome research 21 18758158
2006 Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi. International journal of medical microbiology : IJMM 20 16530476
2023 VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma. Cellular oncology (Dordrecht, Netherlands) 19 36929488
2021 FHL1 Inhibits the Progression of Colorectal Cancer by Regulating the Wnt/β-Catenin Signaling Pathway. Journal of Cancer 19 34335951
2019 FHL1-related clinical, muscle MRI and genetic features in six Chinese patients with reducing body myopathy. Journal of human genetics 19 31273321
2013 Left ventricular hypertrophy caused by a novel nonsense mutation in FHL1. European journal of medical genetics 19 23500067
2013 The evolutionary rewiring of the ribosomal protein transcription pathway modifies the interaction of transcription factor heteromer Ifh1-Fhl1 (interacts with forkhead 1-forkhead-like 1) with the DNA-binding specificity element. The Journal of biological chemistry 19 23625919
2020 FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction. Basic research in cardiology 18 31980934
2020 Structural and Functional Characterization of Host FHL1 Protein Interaction with Hypervariable Domain of Chikungunya Virus nsP3 Protein. Journal of virology 18 33055253
2013 Dysregulation of FHL1 spliceforms due to an indel mutation produces an Emery-Dreifuss muscular dystrophy plus phenotype. Neurogenetics 18 23456229
2008 Identification and characterization of the factor H and FHL-1 binding complement regulator-acquiring surface protein 1 of the Lyme disease spirochete Borrelia spielmanii sp. nov. International journal of medical microbiology : IJMM 18 18706858
2020 Tuning the Functionality by Splicing: Factor H and Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions. Frontiers in immunology 17 33178228
2014 Aggresome-Autophagy Involvement in a Sarcopenic Patient with Rigid Spine Syndrome and a p.C150R Mutation in FHL1 Gene. Frontiers in aging neuroscience 17 25191266
2013 AT1 blockade abolishes left ventricular hypertrophy in heterozygous cMyBP-C null mice: role of FHL1. Fundamental & clinical pharmacology 17 23600722
2009 SLIMMER (FHL1B/KyoT3) interacts with the proapoptotic protein Siva-1 (CD27BP) and delays skeletal myoblast apoptosis. The Journal of biological chemistry 17 19643733
2023 FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design. Nature communications 16 37884534
2021 FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress. Scientific reports 16 34239032
2015 FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest. Molecular medicine reports 16 26017856
2020 MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1. International journal of molecular sciences 15 33322515
2018 A zebrafish model for FHL1-opathy reveals loss-of-function effects of human FHL1 mutations. Neuromuscular disorders : NMD 15 29735270
2018 Aberrant Protein Turn-Over Associated With Myofibrillar Disorganization in FHL1 Knockout Mice. Frontiers in genetics 15 30083183
2012 Fhl1 as a downstream target of Wnt signaling to promote myogenesis of C2C12 cells. Molecular and cellular biochemistry 15 22367176
2018 IGF2-derived miR-483-3p associated with Hirschsprung's disease by targeting FHL1. Journal of cellular and molecular medicine 14 30073757
2016 Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1. Clinical genetics 14 26857240
2016 FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy. Journal of neuromuscular diseases 14 27911330
2022 FHL1 mediates HOXA10 deacetylation via SIRT2 to enhance blastocyst-epithelial adhesion. Cell death discovery 13 36418297
2019 Molecular autopsy and family screening in a young case of sudden cardiac death reveals an unusually severe case of FHL1 related hypertrophic cardiomyopathy. Molecular genetics & genomic medicine 13 31293105
2016 X-linked FHL1 as a novel therapeutic target for head and neck squamous cell carcinoma. Oncotarget 13 26908444
2015 Inhibition of FHL1 inhibits cigarette smoke extract-induced proliferation in pulmonary arterial smooth muscle cells. Molecular medicine reports 13 25975448
2013 Identification of FHL1 as a therapeutic target for Duchenne muscular dystrophy. Human molecular genetics 13 24087791
2007 Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise. Diabetologia 13 17589823

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