Affinage

LUZP1

Leucine zipper protein 1 · UniProt Q86V48

Round 2 corrected
Length
1076 aa
Mass
120.3 kDa
Annotated
2026-04-28
44 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LUZP1 is a leucine zipper-containing cytoskeletal regulatory protein that stabilizes filamentous actin and actomyosin bundles, thereby governing ciliogenesis, cytokinesis, apical constriction, and dendritic spine maturation across multiple cell types. At the centrosome/basal body, LUZP1 suppresses primary cilia formation by stabilizing pericentriolar actin and modulating ARP2 mobilization, and its degradation—driven by truncated SALL1 or the E3 ligase COP1 via the ubiquitin-proteasome pathway—releases this inhibition (PMID:32553112, PMID:32496561, PMID:41937206). During cytokinesis, LUZP1 localizes with the chromosomal passenger complex and inhibits DAPK3-mediated phosphorylation of MYL9 to restrain contractile ring constriction, while at tight junctions it inhibits myosin phosphatase to sustain ppMLC levels and apical constriction (PMID:38009294, PMID:33346378). In vivo, LUZP1 is required for cranial neural tube closure and cardiovascular development in mice, and conditional neuronal deletion impairs dendritic spine maturation, synaptic plasticity, and learning through a filamin A–Rac1–PAK1 axis (PMID:18801334, PMID:40180573).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2001 Medium

    Establishing LUZP1's molecular identity and expression pattern resolved its gene structure and revealed neural-lineage-restricted expression, setting the stage for understanding its developmental role.

    Evidence LacZ knock-in ES cells differentiated in teratomas showed LUZP1 expression restricted to neural lineage cells

    PMID:11702014

    Open questions at the time
    • No functional phenotype was established at this stage
    • Mechanism of neural-restricted expression was not defined
  2. 2008 High

    Knockout mouse studies answered whether LUZP1 is developmentally essential, revealing obligatory roles in cranial neural tube closure and cardiovascular morphogenesis with ectopic Sonic Hedgehog signaling as a molecular consequence.

    Evidence Luzp-null mice exhibited exencephaly, ectopic dorsal Shh expression, elevated apoptosis, and lethal cardiovascular defects

    PMID:18801334

    Open questions at the time
    • Molecular mechanism linking LUZP1 loss to ectopic Shh and neural tube failure was unresolved
    • Whether the cardiovascular defect is cell-autonomous was not determined
  3. 2020 High

    Three independent studies converged to establish LUZP1 as an actin-stabilizing, centrosome-associated protein that suppresses primary ciliogenesis and is regulated by ubiquitin-proteasome degradation, connecting cytoskeletal control to the Townes-Brocks Syndrome protein SALL1.

    Evidence Proximity labeling, co-IP, CRISPR KO, ciliogenesis assays, proteasome inhibitor rescue, and microtubule-associated protein proteomics across multiple labs

    PMID:32496561 PMID:32553112 PMID:33346378

    Open questions at the time
    • Structural basis of LUZP1–actin and LUZP1–EPLIN interaction was not resolved
    • Whether actin stabilization and cilia suppression are separable functions remained unclear
    • Direct evidence that LUZP1 degradation accounts for TBS patient phenotypes was lacking
  4. 2020 High

    Identification of LUZP1 at tight junction-associated circumferential rings answered how it sustains apical contractility: LUZP1 inhibits myosin phosphatase in a microtubule-facilitated manner to maintain ppMLC levels.

    Evidence CRISPR KO in epithelial cells with ppMLC quantification, myosin phosphatase activity assays, and live imaging

    PMID:33346378

    Open questions at the time
    • Identity of the phosphatase subunit directly bound by LUZP1 was not defined
    • Whether this mechanism operates during neural tube closure in vivo was not tested
  5. 2021 Medium

    Discovery of LUZP1 as a tissue-specific component of the CECR2-containing chromatin remodeling complex (CERF) in ES cells linked LUZP1's exencephaly phenotype to chromatin remodeling, broadening its functional repertoire beyond the cytoskeleton.

    Evidence Mass spectrometry of CERF complex components in ES cells versus testes, validated by co-immunoprecipitation

    PMID:34197713

    Open questions at the time
    • Functional consequence of LUZP1 loss on CERF-dependent chromatin remodeling was not tested
    • No reciprocal validation showing LUZP1 depletion destabilizes CERF was provided
    • Whether the CERF association contributes to neural tube closure remains untested
  6. 2023 High

    Live imaging and kinase assays resolved LUZP1's role in cytokinesis: it colocalizes with the chromosomal passenger complex and directly inhibits DAPK3-mediated MYL9 phosphorylation to restrain contractile ring constriction velocity.

    Evidence siRNA knockdown and overexpression, in vitro kinase assay with recombinant DAPK3/MYL9, time-lapse imaging of dividing cells, MS interaction identification

    PMID:38009294

    Open questions at the time
    • Whether LUZP1 directly binds the DAPK3 kinase domain or acts allosterically was not resolved
    • In vivo consequences of accelerated cytokinesis upon LUZP1 loss were not examined
  7. 2024 Medium

    Super-resolution and traction force microscopy established that LUZP1 is essential for concatenation and stacking of myosin II filaments into mature ventral stress fibers, explaining its role in cellular contractility and force generation.

    Evidence CRISPR KO with live-cell imaging of myosin II dynamics, traction force microscopy, super-resolution microscopy

    PMID:38832964

    Open questions at the time
    • Biochemical mechanism by which LUZP1 promotes myosin II stack assembly was not defined
    • Whether this function is separable from LUZP1's DAPK3-inhibitory activity is unclear
  8. 2025 High

    Conditional neuronal knockout demonstrated that LUZP1 controls dendritic spine maturation, synaptic plasticity, and learning via direct interaction with filamin A and modulation of the Rac1–PAK1 pathway, providing a mechanistic basis for its neural-enriched expression.

    Evidence CaMKIIα-Cre conditional KO, co-IP of LUZP1–filamin A, electrophysiology (LTP), Rac1/PAK1 activity assays, behavioral tests

    PMID:40180573

    Open questions at the time
    • Whether filamin A interaction is mediated by LUZP1's leucine zipper domains was not determined
    • Contribution of LUZP1's cilia-suppressive role in neurons versus its spine-maturation function was not dissected
  9. 2026 Medium

    Identification of COP1 as the E3 ligase that ubiquitinates LUZP1, releasing DAPK3-mediated MYL9 phosphorylation, placed LUZP1 in a defined proteolytic regulatory axis with downstream effects on EMT and JAK2-STAT3 signaling in cancer.

    Evidence Ubiquitination assays, co-IP, functional rescue, multi-omics of patient-derived colorectal cancer organoids

    PMID:41937206

    Open questions at the time
    • Structural basis of COP1 recognition of LUZP1 (degron motif) was not mapped
    • Whether COP1-mediated LUZP1 degradation operates in normal developmental contexts is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Unresolved: the structural basis of LUZP1's multivalent interactions (actin, microtubules, DAPK3, filamin A), the relative contribution of its cytoskeletal versus chromatin-remodeling roles to neural tube closure, and whether its leucine zipper motifs mediate specific partner recognition remain open.
  • No structural model of LUZP1 or its complexes exists
  • Separation-of-function alleles distinguishing actin stabilization, cilia suppression, and CERF complex roles have not been generated
  • Whether LUZP1's leucine zippers mediate homo- or heterodimerization relevant to function is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 5 GO:0005815 microtubule organizing center 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1640170 Cell Cycle 1
Partners
ARP2CECR2COP1DAPK3EPLINFLNAMYL9SALL1
Complex memberships
CERF (CECR2-containing chromatin remodeling factor)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 LUZP1 (LUZP) is required for neural tube closure during embryonic brain development. Luzp knockout mice exhibit cranial neural tube closure defects with exposed brain tissues, ectopic Sonic Hedgehog expression in the dorsal lateral neuroepithelium, and elevated apoptosis. LacZ reporter expression driven by the endogenous Luzp promoter was detected in the neuroepithelium and cardiac tissue, and Luzp−/− mice exhibit perinatal death due to complex cardiovascular defects. Knockout mouse (lacZ knock-in reporter), in situ X-gal staining, immunohistochemistry for Sonic Hedgehog, TUNEL apoptosis assay Biochemical and biophysical research communications High 18801334
2001 LUZP1 contains three leucine zipper motifs at its amino terminus, is predominantly expressed in the adult brain, and shows restricted expression in neural lineage cells. Homozygous Luzp-KO/lacZ-KI ES clones differentiate into all three germ layers in teratomas, with lacZ (LUZP) expression restricted to neural lineage cells. Gene targeting/knockout in ES cells, lacZ reporter knock-in, teratoma formation in nude mice, in situ X-gal staining Journal of biomedical science Medium 11702014
2020 LUZP1 is an interactor of truncated SALL1 (the dominantly-acting Townes-Brocks Syndrome protein). LUZP1 localizes around centrioles and to the actin cytoskeleton. Loss of LUZP1 reduces F-actin levels, facilitates primary ciliogenesis, and alters Sonic Hedgehog signaling. Truncated SALL1 promotes ubiquitin-proteasome-mediated degradation of LUZP1, suggesting LUZP1 alterations contribute to TBS etiology. TurboID proximity labeling, pulldown assays, CRISPR/Cas9 knockout, immunofluorescence, ciliogenesis assays, SHH reporter assay, proteasome inhibitor rescue eLife High 32553112
2020 LUZP1 is an actin-stabilizing protein that localizes to actin filaments and the centrosome/basal body. Depletion of LUZP1 or its interacting protein EPLIN increases MyosinVa levels at the centrosome and promotes primary cilia formation. LUZP1 regulates actin dynamics at least in part by mobilizing ARP2 to the centrosome. LUZP1 and EPLIN interact with known ciliogenesis and cilia-length regulators and represent novel players in actin-dependent centrosome-to-basal body conversion. siRNA depletion, immunofluorescence, co-immunoprecipitation, proximity labeling (BioID), ciliogenesis assays, actin dynamics assays The Journal of cell biology High 32496561
2020 LUZP1 is a microtubule-associated protein at tight junction (TJ)-associated circumferential rings (CRs). LUZP1 knockout causes apical constriction defects with reduced di-phosphorylated myosin light chain (ppMLC) levels in CRs. ppMLC promotes LUZP1 recruitment to TJ-associated CRs, where LUZP1 spatiotemporally inhibits myosin phosphatase in a microtubule-facilitated manner, thereby sustaining actomyosin contractility required for vertebrate apical constriction. Unbiased proteomics screening of microtubule-associated proteins in AJC-enriched fractions, CRISPR/Cas9 knockout, live imaging, immunofluorescence, ppMLC quantification, myosin phosphatase activity assays The EMBO journal High 33346378
2021 LUZP1 loss in mouse fibroblasts promotes cell migration and invasion, reduces cell viability, increases apoptosis, increases centriole numbers and nuclear size, and alters actin cytoskeleton organization. LUZP1 loss also changes ACTR3 (ARP3) and phospho-cofilin ratios, implicating LUZP1 in regulating actin polymerization beyond filament bundling. CRISPR/Cas9 knockout, migration/invasion assays (scratch, Transwell), cell viability assay, immunofluorescence, Western blotting for phospho-cofilin and ARP3 Frontiers in cell and developmental biology Medium 33869174
2021 LUZP1 is a component of the CECR2-containing chromatin remodeling factor (CERF) complex in embryonic stem cells but not in testis, demonstrating tissue-specific complex assembly. LUZP1 appears to stabilize the CERF complex in ES cells. This association connects LUZP1 loss-of-function (linked to exencephaly) with the CECR2 chromatin remodeling pathway. Mass spectrometry identification of CERF complex components in ES cells and testes, co-immunoprecipitation validation Biochemistry and cell biology Medium 34197713
2023 LUZP1 colocalizes with the chromosomal passenger complex (CPC) at the centromere in metaphase and at the central spindle in anaphase; these localizations are regulated by CPC activity and KIF20A. LUZP1 interacts with DAPK3 (death-associated protein kinase 3) and MYL9 (myosin light chain 9), and inhibits DAPK3-mediated phosphorylation of MYL9. LUZP1 suppression accelerates contractile ring constriction velocity during cytokinesis, establishing LUZP1 as a novel regulator of cytokinesis. siRNA knockdown, expression plasmid overexpression, immunofluorescence/colocalization, mass spectrometry (interaction identification), kinase assay (MYL9 phosphorylation by DAPK3 ± LUZP1), time-lapse live imaging The FEBS journal High 38009294
2024 LUZP1 plays a central role in the maturation of contractile actomyosin bundles. LUZP1 knockout results in defects in concatenation and persistent association of myosin II filaments, severely impairing assembly of myosin II stacks and thick ventral stress fibers. Loss of LUZP1 causes abnormal cell morphogenesis, migration, and reduced ability to exert forces on the environment (impaired contractility). CRISPR/Cas9 knockout, live-cell imaging of myosin II dynamics, traction force microscopy, immunofluorescence, super-resolution microscopy Cellular and molecular life sciences Medium 38832964
2025 LUZP1 localizes to actin filaments and is highly expressed in CaMKIIα-expressing neurons of the mouse hippocampal dentate gyrus. LUZP1 depletion impedes dendritic spine maturation (excess filopodia, loss of mushroom spines), reduces spontaneous electrical activity and synaptic plasticity. Conditional deletion of LUZP1 in CaMKIIα neurons impairs learning and memory. Mechanistically, LUZP1 controls dendritic maturation by directly interacting with filamin A and modulating the Rac1-PAK1 signaling pathway. Conditional knockout (CaMKIIα-Cre), shRNA knockdown, co-immunoprecipitation (LUZP1–filamin A interaction), immunofluorescence, electrophysiology (LTP), behavioral assays (learning and memory), Rac1/PAK1 activity assays The Journal of neuroscience High 40180573
2026 The E3 ubiquitin ligase COP1 ubiquitinates and degrades LUZP1, thereby releasing DAPK3 from LUZP1-mediated suppression, leading to enhanced MYL9 phosphorylation and activation of EMT and JAK2-STAT3-CCND2 signaling. This establishes a COP1-LUZP1-DAPK3-MYL9 regulatory axis relevant to colorectal cancer liver metastasis and oxaliplatin resistance. In vitro and in vivo functional experiments, co-immunoprecipitation, ubiquitination assays, multi-omics (WES, bulk RNA-seq, scRNA-seq) of patient-derived organoids, Western blotting Experimental hematology & oncology Medium 41937206
2026 NF-κB acts as an upstream transcriptional regulator of LUZP1 expression: NF-κB inhibition reduces LUZP1 expression, while stimulation with IL-1β or TNF-α induces LUZP1 upregulation and rescues the migration defect caused by LUZP1 depletion. LUZP1 knockdown impairs migration, invasion, invadopodia formation, and EMT, while enhancing sensitivity to docetaxel and cisplatin. shRNA knockdown, NF-κB pathway inhibition/stimulation, migration/invasion assays, invadopodia formation assays, drug sensitivity assays, Western blotting Oncology reports Medium 41952496

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2008 Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry. Journal of proteome research 148 18570454
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2017 The human cytoplasmic dynein interactome reveals novel activators of motility. eLife 118 28718761
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2021 FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2. Molecular cancer 106 33658012
2021 Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling. Molecular cell 105 33545068
2008 LUZP deficiency affects neural tube closure during brain development. Biochemical and biophysical research communications 35 18801334
2020 LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome. eLife 31 32553112
2020 LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation. The Journal of cell biology 28 32496561
2020 A microtubule-LUZP1 association around tight junction promotes epithelial cell apical constriction. The EMBO journal 17 33346378
2021 LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton. Frontiers in cell and developmental biology 13 33869174
2001 Restricted expression of LUZP in neural lineage cells: a study in embryonic stem cells. Journal of biomedical science 13 11702014
2021 The Circ_0001367/miR-545-3p/LUZP1 Axis Regulates Cell Proliferation, Migration and Invasion in Glioma Cells. Frontiers in oncology 11 34869035
2021 Chromatin remodeling factor CECR2 forms tissue-specific complexes with CCAR2 and LUZP1. Biochemistry and cell biology = Biochimie et biologie cellulaire 7 34197713
2022 LUZP1: A new player in the actin-microtubule cross-talk. European journal of cell biology 5 35738212
2023 Leucine zipper protein 1 (LUZP1) regulates the constriction velocity of the contractile ring during cytokinesis. The FEBS journal 3 38009294
2024 LUZP1 regulates the maturation of contractile actomyosin bundles. Cellular and molecular life sciences : CMLS 2 38832964
2026 Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation. Experimental hematology & oncology 0 41937206
2026 NF‑κB‑driven LUZP1 promotes metastasis and chemoresistance in head and neck squamous cell carcinoma. Oncology reports 0 41952496
2025 LUZP1 Regulates Dendritic Spine Maturation and Synaptic Plasticity in the Hippocampal Dentate Gyrus of Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 40180573