Affinage

CHL1

Neural cell adhesion molecule L1-like protein · UniProt O00533

Length
1208 aa
Mass
135.1 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHL1 is a transmembrane immunoglobulin-superfamily cell adhesion molecule that orchestrates axon guidance, neurite outgrowth, synaptic vesicle recycling, and neural progenitor proliferation through multiple signaling mechanisms. Its extracellular domain undergoes regulated ectodomain shedding by ADAM8 and BACE1 (at Gln1061-Asp1062), releasing soluble fragments that promote neuronal survival and neurite outgrowth (PMID:14761956, PMID:22692213, PMID:22988240). Intracellularly, CHL1 recruits ezrin via a cytoplasmic RGGKYSV motif to mediate Sema3A-induced growth cone collapse, binds Hsc70 to regulate clathrin-dependent synaptic vesicle recycling, and forms a signaling complex with NB-3 and PTPα to orient apical dendrites, while negatively regulating neural progenitor proliferation through ERK1/2 MAPK (PMID:17995939, PMID:17178404, PMID:18046458, PMID:20933598). Ligand-dependent clustering triggers palmitoylation at Cys-1102 and lipid raft endocytosis involving βII spectrin dissociation, coupling surface dynamics to neuritogenesis via L-type Ca²⁺ channels (PMID:23144456).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1999 Medium

    Establishing that soluble CHL1 ectodomain functions as a neuronal survival factor answered whether CHL1 has signaling roles beyond static adhesion, linking it to Bcl-2-mediated anti-apoptotic protection.

    Evidence CHL1-Fc fusion protein treatment of serum-deprived cerebellar and hippocampal neurons with Bcl-2 Western blot

    PMID:10022583

    Open questions at the time
    • Single lab without genetic validation of survival phenotype
    • Receptor or binding partner mediating survival signal not identified
    • Downstream pathway between CHL1 engagement and Bcl-2 upregulation not mapped
  2. 2004 High

    Identification of ADAM8 as the specific sheddase that cleaves CHL1 at two fibronectin-domain sites established that CHL1 undergoes regulated proteolytic processing to release biologically active soluble fragments promoting neurite outgrowth.

    Evidence In vitro cleavage reconstitution with wild-type and catalytic-dead ADAM8, ADAM8-KO brain extracts, neurite outgrowth co-culture

    PMID:14761956

    Open questions at the time
    • Physiological signals that trigger ADAM8-mediated shedding in vivo unknown
    • Relative contributions of ADAM8 vs BACE1 cleavage not resolved
  3. 2006 High

    Discovery that CHL1 recruits Hsc70 to synaptic membranes and that CHL1 deficiency causes accumulation of clathrin-coated vesicles revealed an unexpected function for a cell adhesion molecule in clathrin-dependent synaptic vesicle recycling.

    Evidence CHL1-KO mice, synaptic vesicle fractionation, FM dye recycling assay, electron microscopy of coated vesicles

    PMID:17178404

    Open questions at the time
    • CHL1 domain or motif mediating Hsc70 recruitment not mapped
    • Whether CHL1-Hsc70 interaction is regulated by neuronal activity unknown
  4. 2007 High

    Three concurrent advances defined CHL1's cytoplasmic signaling: the RGGKYSV motif recruits ERM proteins for Sema3A-induced growth cone collapse; CHL1 forms a ternary complex with NB-3 and PTPα to orient cortical dendrites; and CHL1 expressed on reactive astrocytes restricts axon regeneration via homophilic interaction, collectively establishing CHL1 as a multifunctional signaling hub in neural development and injury.

    Evidence Site-directed mutagenesis of RGGKYSV motif with growth cone collapse assay; reciprocal co-IP plus triple-KO dendritic orientation analysis; CHL1-KO spinal cord injury model with astrocyte co-culture

    PMID:17611275 PMID:17995939 PMID:18046458

    Open questions at the time
    • How CHL1-ERM and CHL1-NB-3/PTPα pathways are coordinated in the same neuron unknown
    • Downstream effectors of PTPα activity in dendrite orientation not identified
  5. 2010 High

    CHL1 cooperates with L1 through selective EphA7 association to guide thalamocortical axons, and separately acts as a negative regulator of neural progenitor proliferation via ERK1/2 MAPK, expanding CHL1's roles from post-mitotic neurons to progenitor cell biology.

    Evidence CHL1/L1 double-KO mice with thalamocortical tracing and EphrinA5 growth cone collapse; CHL1-KO NPC BrdU labeling with ERK inhibitor epistasis

    PMID:20576928 PMID:20933598

    Open questions at the time
    • Mechanism by which CHL1 suppresses ERK1/2 activation in progenitors not defined
    • Whether EphA7 directly phosphorylates CHL1 or signals through it indirectly unknown
  6. 2012 High

    BACE1 was identified as a second in vivo sheddase cleaving CHL1 at Gln1061-Asp1062, with BACE1-KO mice phenocopying CHL1-KO axon guidance defects, and palmitoylation of Cys-1102 was shown to drive lipid raft endocytosis coupled to βII spectrin dissociation during neuritogenesis—together linking surface dynamics and proteolytic processing to CHL1 function.

    Evidence Quantitative secretome proteomics with BACE1 inhibition/KO and MS cleavage-site mapping; C1102 mutagenesis, palmitoylation assay, βII spectrin co-IP, lipid raft disruption pharmacology

    PMID:22692213 PMID:22988240 PMID:23144456

    Open questions at the time
    • Whether ADAM8 and BACE1 act sequentially or independently on the same CHL1 pool unknown
    • Palmitoyl transferase responsible for CHL1 palmitoylation not identified
    • Structural basis of βII spectrin-CHL1 interaction not determined
  7. 2019 Medium

    Identification of ALCAM as a trans-heterophilic ligand for CHL1 that promotes midbrain dopamine neuron axon growth and modulates semaphorin responses extended CHL1's ligand repertoire beyond homophilic binding.

    Evidence Primary midbrain cultures on ALCAM substrate with neutralizing antibodies against CHL1, L1cam, and Nrp1

    PMID:31300520

    Open questions at the time
    • Direct biophysical binding parameters for CHL1-ALCAM not determined
    • In vivo significance for dopaminergic circuit wiring not demonstrated
  8. 2020 High

    Demonstration that TET1-mediated promoter demethylation activates CHL1 transcription and that CHL1 suppresses Hedgehog signaling revealed an epigenetic-CHL1-Hedgehog axis relevant to cancer biology, extending CHL1 function beyond the nervous system.

    Evidence ChIP-seq, bisulfite sequencing, TET1 silencing/overexpression, CHL1 overexpression with Hedgehog inhibitor rescue in pancreatic cancer models

    PMID:32753651

    Open questions at the time
    • Molecular target through which CHL1 inhibits Hedgehog pathway not identified
    • Whether CHL1 adhesion or shedding is required for Hedgehog suppression unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which CHL1 integrates its multiple cytoplasmic signaling outputs (ERM recruitment, Hsc70 binding, βII spectrin association, ERK modulation) in the same cell remains undefined, and the structural basis for CHL1's selective trans interactions with ALCAM, NB-3, and EphA7 is unresolved.
  • No crystal or cryo-EM structure of CHL1 extracellular or intracellular domains
  • No reconstituted signaling system integrating multiple CHL1 effector pathways
  • In vivo relevance of ALCAM interaction for dopaminergic circuit assembly not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-112316 Neuronal System 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ADAM8ALCAMBACE1CNTN6EPHA7HSPA8PTPRASPTBN1
Complex memberships
CHL1-NB-3-PTPα complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 CHL1 is cleaved by BACE1 protease in vivo at the membrane-proximal region between Gln1061 and Asp1062, as determined by quantitative proteomics of the neuronal secretome after BACE1 inhibition, genetic BACE1 knockout, and mass spectrometry mapping of the cleavage site. Quantitative secretome proteomics, BACE1 knockout mice, pharmacological BACE1 inhibition, mass spectrometry cleavage-site mapping The Journal of biological chemistry High 22692213 22988240
2012 BACE1-deficient mice exhibit axon guidance defects (shortened/disorganized infrapyramidal bundle of mossy fibers; olfactory sensory neuron projection defects) that are strikingly similar to CHL1-deficient mice, establishing that CHL1 is a physiological BACE1 substrate in hippocampus and olfactory bulb, and that loss of BACE1 processing of CHL1 underlies these axon guidance phenotypes. Genetic knockout comparison (BACE1-/- vs CHL1-/- mice), co-localization immunostaining, in vivo processing assays The Journal of biological chemistry High 22988240
2004 ADAM8 metalloprotease cleaves CHL1 ectodomain at two sites within fibronectin domains II and V (yielding 125 kDa and 165 kDa fragments), releasing soluble CHL1 that promotes neurite outgrowth and suppresses neuronal cell death; catalytically inactive ADAM8 (E330Q) and ADAM10/ADAM17 do not cleave CHL1. In vitro cleavage assay with CHL1-Fc fusion protein, transfection with wild-type and catalytic-dead ADAM8, ADAM8-deficient mouse brain extracts, co-culture neurite outgrowth assay The Journal of biological chemistry High 14761956
2006 The intracellular domain of CHL1 binds the clathrin-uncoating ATPase Hsc70; CHL1 targets Hsc70 to the synaptic plasma membrane and synaptic vesicles; CHL1 deficiency or disruption of the CHL1/Hsc70 complex causes accumulation of clathrin-coated synaptic vesicles, impairs clathrin release, and reduces activity-dependent FM dye uptake/release, establishing CHL1 as a regulator of clathrin-dependent synaptic vesicle recycling. Binding partner identification (pulldown/interaction screen), CHL1 knockout mice, synaptic vesicle fractionation, FM dye recycling assay, electron microscopy of coated vesicles Neuron High 17178404
2007 CHL1 directly associates with NB-3 (F3/contactin family) and enhances its cell surface expression; both CHL1 and NB-3 interact with protein tyrosine phosphatase alpha (PTPα) and regulate its activity; this CHL1-NB-3-PTPα signaling complex mediates correct apical dendrite orientation of deep-layer pyramidal neurons in the developing neocortex. Co-immunoprecipitation, cell surface expression assays, PTPα activity assay, CHL1-/- and NB-3-/- and PTPα-/- knockout mouse phenotypic analysis The EMBO journal High 18046458
2007 CHL1 recruits ezrin (ERM family) to the plasma membrane via a membrane-proximal cytoplasmic motif (RGGKYSV); this CHL1/ERM interaction is required for Sema3A-induced growth cone collapse, CHL1-dependent neurite outgrowth and branching, haptotactic cell migration, and adhesion to fibronectin in cortical neurons. Cytofluorescence recruitment assay, site-directed mutagenesis of RGGKYSV motif, growth cone collapse assay, neurite outgrowth assay, migration/adhesion assays Journal of neurochemistry High 17995939
2010 CHL1 associates selectively with EphA7 (whereas L1 associates with EphA3, EphA4, and EphA7); CHL1-/- and L1-/y double-mutant mice show a striking posterior shift of motor thalamic axons to visual cortex not seen in single mutants; both L1 and CHL1 are required for repellent responses to EphrinA5 in growth cone collapse assays, establishing cooperative L1/CHL1-EphA receptor signaling in thalamocortical topographic targeting. Co-immunoprecipitation, CHL1-/-/L1-/y double-knockout mice, growth cone collapse assay with EphrinA5, thalamocortical axon tracing Cerebral cortex High 20576928
2007 CHL1 expression is upregulated in GFAP-positive astrocytes at the spinal cord lesion core after injury; this upregulation is induced by FGF2 via FGF receptor-dependent ERK, CaMK, and PI3K signaling; CHL1-/- mice show improved functional recovery after spinal cord compression with enhanced monoaminergic reinnervation; homophilic CHL1-CHL1 interaction between neurons and astrocytes reduces neurite outgrowth, establishing CHL1 as a glial scar component that restricts axonal regeneration. CHL1-/- knockout mice, spinal cord compression injury model, locomotor rating, immunohistochemistry, astrocyte cultures with signaling inhibitors, neuron-astrocyte co-culture neurite assay The Journal of neuroscience High 17611275
2010 CHL1 deficiency increases proliferation and self-renewal of neural progenitor cells (NPCs) and enhances neuronal differentiation; this is mediated through enhanced activation of ERK1/2 MAPK, and pharmacological inhibition of ERK1/2 eliminates the proliferative effect of CHL1 deficiency, placing CHL1 upstream of ERK1/2 MAPK as a negative regulator of NPC proliferation. CHL1-/- knockout mice, BrdU labeling in vivo, NPC isolation and culture, ERK1/2 inhibitor experiments, Western blot for ERK1/2 activation Molecular and cellular neurosciences High 20933598
2012 Neuritogenesis-promoting ligand-dependent clustering of CHL1 induces palmitoylation of CHL1 and lipid raft-dependent endocytosis; βII spectrin is identified as a binding partner of CHL1 and partial disruption of the CHL1-βII spectrin complex accompanies endocytosis; mutation of Cys-1102 in the intracellular domain abolishes palmitoylation and reduces endocytosis; CHL1-dependent neurite outgrowth requires lipid raft assembly and L-type voltage-dependent Ca2+ channels. Co-immunoprecipitation of βII spectrin, palmitoylation assay, site-directed mutagenesis (C1102), lipid raft disruption pharmacology, Ca2+ channel inhibitor (nifedipine), neurite outgrowth assay The Journal of biological chemistry High 23144456
1999 CHL1-Fc fusion protein (extracellular domain fused to human IgG Fc) significantly enhances survival of cerebellar granule neurons and hippocampal neurons undergoing apoptosis in serum-free culture; CHL1-mediated survival is associated with increased Bcl-2 protein levels in neurons. Neuronal survival assay, CHL1-Fc fusion protein treatment (soluble and substrate), Western blot for Bcl-2 and c-Jun Journal of neurobiology Medium 10022583
2005 CHL1-Fc fusion protein promotes survival of purified embryonic motoneurons; CHL1-mediated motoneuron survival is completely inhibited by LY294002 (PI3K inhibitor) and PD98059 (MEK inhibitor), indicating that both MEK/ERK and PI3K pathways are required for CHL1 survival signaling; effects of CHL1 and FGF-2 on motoneurons are additive at suboptimal concentrations, suggesting shared signaling through FGFR. Purified motoneuron survival assay, pharmacological inhibitors of PI3K and MEK, dose-response analysis, FGF-2 combination experiments Journal of neuroscience research Medium 15880726
2019 CHL1 functions in trans-heterophilic interaction with ALCAM (CD166) substrate to promote midbrain dopamine (mDA) neuron axon growth; neutralizing antibodies against CHL1, L1cam, or Nrp1 abolish the ALCAM growth-promoting effect; ALCAM substrate modulates mDA neurite response to soluble semaphorins (Sema3A and Sema3C) in a CHL1-dependent manner. Primary midbrain cultures, neutralizing antibody blockade, ALCAM substrate assay, semaphorin response assay The Journal of neuroscience Medium 31300520
2020 TET1 promotes CHL1 transcription by binding and demethylating the CHL1 promoter; CHL1 overexpression inhibits the Hedgehog signaling pathway; TET1 silencing-induced chemoresistance and EMT in pancreatic ductal adenocarcinoma are reversed by CHL1 overexpression or Hedgehog pathway inhibitor (GDC-0449), placing CHL1 downstream of TET1-mediated demethylation and upstream of Hedgehog pathway inhibition. RNA-seq, whole genome bisulfite sequencing, ChIP-seq, TET1 silencing/overexpression, CHL1 overexpression, in vitro and in vivo functional assays, Hedgehog inhibitor treatment Oncogene High 32753651
1997 Human homologs of yeast CHL1 (hCHLR1 and hCHLR2) are expressed only in proliferating cells, with expression beginning at S-phase entry; in vitro translated hCHLR1 binds both single- and double-stranded DNA; hCHLR proteins localize to the nucleolus by immunofluorescence and cell fractionation. Cell fractionation, indirect immunofluorescence, in vitro DNA binding assay, cell cycle re-entry experiments with serum stimulation, differentiation assays The Journal of biological chemistry Medium 9013641
2000 Yeast CHL1 encodes a nuclear protein with an essential ATP binding site; site-directed mutagenesis of the ATP binding site inactivates CHL1 function in chromosome segregation; overexpression of ATP-binding mutants acts as dominant negative to interfere with chromosome transmission; CHL1 function is disproportionately critical for segregation of small chromosomes (<150 kb). Site-directed mutagenesis of ATP-binding site, chromosome transmission fidelity assay, dominant-negative overexpression, nuclear fractionation, polyclonal antibody staining Nucleic acids research Medium 10931920
2013 Yeast Chl1 helicase promotes Scc2 (cohesin loader) loading onto chromatin specifically during S-phase but not G1; both Scc2 and cohesin enrichment at chromatin are defective in chl1 mutant cells; Chl1 expression and chromatin recruitment peak during S-phase; G1-loaded cohesins are insufficient for cohesion, establishing Chl1 as an S-phase-specific regulator of cohesin deposition during DNA replication. Chromatin immunoprecipitation (ChIP), kinetic ChIP through cell cycle, co-immunoprecipitation, cell cycle synchronization experiments PloS one Medium 24086532
2011 Yeast Chl1p is required for establishment of sister chromatid cohesion (SCC) during S-phase and maintenance of SCC in G2; chl1 mutant cells have only ~25% of normal cohesin subunit Scc1p at centromeres; chl1 mutation causes spindle elongation (~60-80% longer) under replication stress (hydroxyurea arrest) due to reduced pericentromeric cohesion; kinetochore-microtubule interactions remain intact in chl1 mutants. Spindle length measurement, cohesin ChIP at centromeres, hydroxyurea arrest experiments, kinetochore function assays, cell viability assays BMC genetics Medium 21943249
2017 miR-151a-3p directly regulates CHL1 expression via its 3'UTR as shown by luciferase reporter assay; overexpression of miR-151a-3p increases cell sensitivity to the SSRI paroxetine via CHL1 downregulation in human lymphoblastoid cell lines. Luciferase 3'UTR reporter assay, miRNA overexpression, paroxetine sensitivity phenotyping Frontiers in molecular neuroscience Medium 29163031
2000 CHL1 mRNA is strongly upregulated in thalamic reticular nucleus neurons that regenerate axons into peripheral nerve grafts but not in neurons failing to regenerate; CHL1 upregulation is sustained (3 days to 10 weeks) only in regenerating neurons, establishing CHL1 as part of the regeneration-associated gene expression program in CNS neurons. In situ hybridization, retrograde labeling from nerve grafts, comparison of living vs freeze-killed grafts The Journal of comparative neurology Medium 10972939
2003 Glial cells upregulate CHL1 expression in response to optic nerve crush injury; a single intravitreal FGF-2 injection increases CHL1 in retinal astrocytes and Müller cells, establishing FGF-2 as a regulator of CHL1 expression in injured CNS glia. Optic nerve crush model, intravitreal FGF-2 injection, immunohistochemistry, Western blot Journal of neuroscience research Low 12605410

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The variant call format and VCFtools. Bioinformatics (Oxford, England) 10624 21653522
2013 Frailty consensus: a call to action. Journal of the American Medical Directors Association 2863 23764209
2003 From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 1946 14530185
2009 CHL1 functions as a nitrate sensor in plants. Cell 935 19766570
2007 Regenerative endodontics: a review of current status and a call for action. Journal of endodontics 586 17368324
2021 Resveratrol (RV): A pharmacological review and call for further research. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 334 34649335
2008 Environmental epigenetics and asthma: current concepts and call for studies. American journal of respiratory and critical care medicine 196 18187692
1991 Pathobiology of endothelial and other vascular cells in diabetes mellitus. Call for data. Diabetes 167 2040380
2006 Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. American journal of respiratory and critical care medicine 156 17053206
2024 Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy. Journal of hematology & oncology 148 38863020
2012 The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo. The Journal of biological chemistry 148 22692213
1999 Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1. Journal of neurobiology 148 10022583
2012 β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)-deficient mice exhibit a close homolog of L1 (CHL1) loss-of-function phenotype involving axon guidance defects. The Journal of biological chemistry 129 22988240
2016 Plant Enhancers: A Call for Discovery. Trends in plant science 107 27593567
2004 Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease-disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death. The Journal of biological chemistry 106 14761956
2000 Differential expression of COUP-TFI, CHL1, and two novel genes in developing neocortex identified by differential display PCR. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 11027229
2018 Cancer genetics, precision prevention and a call to action. Nature genetics 98 30158684
2004 Developing DNA vaccines that call to dendritic cells. The Journal of clinical investigation 92 15520855
2000 Clues to patients' explanations and concerns about their illnesses. A call for active listening. Archives of family medicine 91 10728107
2007 Glial scar expression of CHL1, the close homolog of the adhesion molecule L1, limits recovery after spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 17611275
2007 Eradication of cross-contaminated cell lines: a call for action. Cell biology and toxicology 85 17522957
2014 MicroRNA-590 promotes cervical cancer cell growth and invasion by targeting CHL1. Journal of cellular biochemistry 77 24288179
2011 Differential expression of CHL1 gene during development of major human cancers. PloS one 75 21408220
2006 The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron 75 17178404
2007 Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTP alpha. The EMBO journal 74 18046458
2002 The Arabidopsis dual-affinity nitrate transporter gene AtNRT1.1 (CHL1) is regulated by auxin in both shoots and roots. Journal of experimental botany 70 11912226
2014 FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World journal of gastroenterology 69 25132748
2021 Skeletal Muscle Damage in COVID-19: A Call for Action. Medicina (Kaunas, Lithuania) 67 33921429
2016 The Preoperative Sinus CT: Avoiding a "CLOSE" Call with Surgical Complications. Radiology 67 27643765
2017 microRNAs Make the Call in Cancer Personalized Medicine. Frontiers in cell and developmental biology 64 29018797
2007 Plasticity and heterogeneity of lymphoid organs. What are the criteria to call a lymphoid organ primary, secondary or tertiary? Immunology letters 62 17698207
2011 Molecular call and response: the physiology of bacterial small RNAs. Biochimica et biophysica acta 61 21843668
2017 A wake-up call to quiescent cancer cells - potential use of DYRK1B inhibitors in cancer therapy. The FEBS journal 58 29193696
2005 Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population. Schizophrenia research 58 15653271
2018 The African Esophageal Cancer Consortium: A Call to Action. Journal of global oncology 57 30241229
2004 Call for an enzyme genomics initiative. Genome biology 57 15287973
2017 Analyzing DNA Nanotechnology: A Call to Arms For The Analytical Chemistry Community. Analytical chemistry 56 28207239
2021 Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence. Journal of molecular medicine (Berlin, Germany) 53 34800164
2011 Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. Pharmacogenomics 50 21332311
2007 CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane. Journal of neurochemistry 50 17995939
2021 Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway. Cell death & disease 49 34718336
2018 Translational Research in Cardiovascular Repair: A Call for a Paradigm Shift. Circulation research 49 29348252
2016 Melanoma: Last call for radiotherapy. Critical reviews in oncology/hematology 49 28109401
2010 L1 and CHL1 Cooperate in Thalamocortical Axon Targeting. Cerebral cortex (New York, N.Y. : 1991) 48 20576928
2006 Repulsion or adhesion: receptors make the call. Current opinion in cell biology 48 16930978
2021 Capturing outcomes of competency-based medical education: The call and the challenge. Medical teacher 47 34121596
2011 A call for standardized naming and reporting of human ESC and iPSC lines. Cell stem cell 47 21474098
2023 A pharmacological review on SIRT 1 and SIRT 2 proteins, activators, and inhibitors: Call for further research. International journal of biological macromolecules 46 37105251
2018 Overexpression of miR-21-5p promotes proliferation and invasion of colon adenocarcinoma cells through targeting CHL1. Molecular medicine (Cambridge, Mass.) 43 30134821
2014 miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochemical and biophysical research communications 41 24971532
2012 Circadian regulation of bird song, call, and locomotor behavior by pineal melatonin in the zebra finch. Journal of biological rhythms 41 22476775
2013 CHL1 is involved in human breast tumorigenesis and progression. Biochemical and biophysical research communications 38 23906755
2019 Schizophrenia as a pseudogenetic disease: A call for more gene-environmental studies. Psychiatry research 37 31200193
1999 Exercise clinical trials in cancer prevention research: a call to action. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 37 10090297
2013 Chl1 DNA helicase regulates Scc2 deposition specifically during DNA-replication in Saccharomyces cerevisiae. PloS one 36 24086532
2012 The phosphatidylinositol 4-kinases: don't call it a comeback. Sub-cellular biochemistry 36 22403072
2000 CHL1 is a nuclear protein with an essential ATP binding site that exhibits a size-dependent effect on chromosome segregation. Nucleic acids research 36 10931920
2017 Genome-Scale Data Call for a Taxonomic Rearrangement of Geodermatophilaceae. Frontiers in microbiology 35 29312207
2016 Unsolved matters in leprosy: a descriptive review and call for further research. Annals of clinical microbiology and antimicrobials 35 27209077
2013 Championing person-first language: a call to psychiatric mental health nurses. Journal of the American Psychiatric Nurses Association 35 23698977
1997 Characterization of putative human homologues of the yeast chromosome transmission fidelity gene, CHL1. The Journal of biological chemistry 34 9013641
2013 A call to ARMS: targeting the PAX3-FOXO1 gene in alveolar rhabdomyosarcoma. Expert opinion on therapeutic targets 33 23432728
2010 CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway. Molecular and cellular neurosciences 33 20933598
2006 Obtaining and screening compound collections: a user's guide and a call to chemists. Current opinion in chemical biology 33 16677847
2014 Bioremediation of chlorimuron-ethyl-contaminated soil by Hansschlegelia sp. strain CHL1 and the changes of indigenous microbial population and N-cycling function genes during the bioremediation process. Journal of hazardous materials 32 24794985
2005 Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons. Journal of neuroscience research 31 15880726
2023 Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions. ACS nano 30 36988207
2021 Recognizing the ethical implications of stem cell research: A call for broadening the scope. Stem cell reports 30 34214488
2021 Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis. International journal of nanomedicine 30 34408418
2020 An appraisal of allergic disorders in India and an urgent call for action. The World Allergy Organization journal 29 32774662
2019 Axonal Growth of Midbrain Dopamine Neurons is Modulated by the Cell Adhesion Molecule ALCAM Through Trans-Heterophilic Interactions with L1cam, Chl1, and Semaphorins. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 31300520
2019 The cell stress response: extreme times call for post-transcriptional measures. Wiley interdisciplinary reviews. RNA 29 31755249
2012 Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis. The Journal of biological chemistry 29 23144456
2002 Endotracheal epinephrine: a call for larger doses. Anesthesia and analgesia 29 12351290
2018 Microbes and Alzheimer's Disease: New Findings Call for a Paradigm Change. Trends in neurosciences 28 30033181
2000 The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons. The Journal of comparative neurology 28 10972939
2025 Treatment of patients with IgA nephropathy: a call for a new paradigm. Kidney international 27 39894081
2021 Anal cancer and precancerous lesions: a call for improvement. The lancet. Gastroenterology & hepatology 27 33714370
2021 The ethics of human-embryoids model: a call for consistency. Journal of molecular medicine (Berlin, Germany) 27 33792755
2012 So what do we call GPR18 now? British journal of pharmacology 27 22014123
1996 The human homologue of the yeast CHL1 gene is a novel keratinocyte growth factor-regulated gene. The Journal of biological chemistry 27 8798685
2015 Cervical cancer control in Latin America: A call to action. Cancer 26 26670695
2018 A call for more science in forensic science. Proceedings of the National Academy of Sciences of the United States of America 25 29650539
2003 Altered expression of CHL1 by glial cells in response to optic nerve injury and intravitreal application of fibroblast growth factor-2. Journal of neuroscience research 25 12605410
2013 Cutaneous toxicities of BRAF inhibitors: clinical and pathological challenges and call to action. Critical reviews in oncology/hematology 23 23830782
2019 Atlas-CNV: a validated approach to call single-exon CNVs in the eMERGESeq gene panel. Genetics in medicine : official journal of the American College of Medical Genetics 22 30890783
2011 Functional characterization of the Saccharomyces cerevisiae protein Chl1 reveals the role of sister chromatid cohesion in the maintenance of spindle length during S-phase arrest. BMC genetics 22 21943249
2022 Review of Cerebrospinal Fluid Physiology and Dynamics: A Call for Medical Education Reform. Neurosurgery 21 35522666
2011 Living in a box or call of the wild? Revisiting lifetime inactivity and sarcopenia. Antioxidants & redox signaling 21 21539480
2024 Brain incoming call from glia during neuroinflammation: Roles of extracellular vesicles. Neurobiology of disease 20 39251030
2017 MicroRNA-Mediated Regulation of ITGB3 and CHL1 Is Implicated in SSRI Action. Frontiers in molecular neuroscience 20 29163031
2013 To call or not to call--that is the question (while driving). Accident; analysis and prevention 20 23612559
2007 Neuroethology of female preference in the synchronously singing bushcricket Mecopoda elongata (Tettigoniidae; Orthoptera): why do followers call at all? The Journal of experimental biology 20 17234616
2020 From patient satisfaction to patient experience: A call to action for nursing in China. Journal of nursing management 19 31793108
2017 CHL1 Is Expressed and Functions as a Malignancy Promoter in Glioma Cells. Frontiers in molecular neuroscience 19 29089868
2012 Parenteral nutrition and calorie delivery in the ICU: controversy, clarity, or call to action? Current opinion in critical care 19 22343307
2025 SPP1 macrophages across diseases: A call for reclassification? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 40047497
2020 TET1 downregulates epithelial-mesenchymal transition and chemoresistance in PDAC by demethylating CHL1 to inhibit the Hedgehog signaling pathway. Oncogene 18 32753651
2013 Impaired interval timing and spatial-temporal integration in mice deficient in CHL1, a gene associated with schizophrenia. Timing & time perception (Leiden, Netherlands) 17 28890867
2020 Pharmacogenetics in psychiatric care, a call for uptake of available applications. Psychiatry research 16 32739644