Affinage

LUZP1

Leucine zipper protein 1 · UniProt Q86V48

Length
1076 aa
Mass
120.3 kDa
Annotated
2026-06-10
14 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LUZP1 is an actin-stabilizing, leucine zipper protein that organizes the actomyosin cytoskeleton across diverse cellular contexts, controlling cilium formation, epithelial constriction, cytokinesis, and neuronal architecture (PMID:32496561, PMID:33346378, PMID:38009294). At centrosomes and basal bodies it stabilizes F-actin and negatively regulates primary ciliogenesis, in part by mobilizing ARP2 to the centrosome and restraining MyosinVa accumulation, thereby shaping Sonic Hedgehog signaling output (PMID:32553112, PMID:32496561). At the level of contractile machinery, LUZP1 promotes the maturation of thick actomyosin bundles by limiting persistent myosin II filament association and stack assembly (PMID:38832964), and it tunes phosphorylated myosin light chain: at tight-junction-associated actomyosin rings it inhibits myosin phosphatase to sustain di-phosphorylated MLC and drive apical constriction (PMID:33346378), while during cytokinesis it interacts with DAPK3 and inhibits DAPK3-mediated MYL9 phosphorylation to restrain contractile ring constriction (PMID:38009294). In neurons it localizes to actin in hippocampal neurons and directs dendritic spine maturation through direct interaction with filamin A and modulation of Rac1-PAK1 signaling, with conditional loss impairing synaptic plasticity, learning, and memory (PMID:40180573). LUZP1 abundance is set by transcriptional induction via NF-κB and by proteasomal turnover through the E3 ligase COP1, and its degradation releases DAPK3 to promote MYL9 phosphorylation and pro-metastatic signaling in colorectal cancer (PMID:41937206, PMID:41952496). At the organismal level, Luzp1 loss in mice causes cranial neural tube closure defects with ectopic Sonic Hedgehog expression (PMID:18801334), and LUZP1 also functions as a tissue-specific subunit of the CECR2-containing CERF chromatin remodeling complex in embryonic stem cells (PMID:34197713).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2008 Medium

    Established LUZP1 as developmentally essential by showing its loss disrupts a defined morphogenetic process rather than being dispensable.

    Evidence Luzp knockout mouse with lacZ reporter, Shh immunohistochemistry, and TUNEL apoptosis assay

    PMID:18801334

    Open questions at the time
    • Did not identify the molecular activity of LUZP1 underlying neural tube closure
    • Link between LUZP1 and ectopic Shh expression was correlative, not mechanistic
  2. 2020 High

    Defined LUZP1's core molecular identity as an actin-stabilizing protein at centrosomes that negatively regulates ciliogenesis, resolving how its loss could perturb Shh signaling.

    Evidence TurboID proximity labeling, pulldowns, siRNA/CRISPR loss-of-function, F-actin and ciliogenesis assays, Shh reporter, and ARP2/MyosinVa recruitment assays in cultured cells

    PMID:32496561 PMID:32553112

    Open questions at the time
    • Mechanism by which LUZP1 mobilizes ARP2 to centrosomes not resolved structurally
    • Relationship between actin stabilization and cilia suppression not fully separated
  3. 2020 High

    Connected LUZP1 to epithelial mechanics by showing it sustains myosin phosphorylation at tight-junction actomyosin rings to drive apical constriction.

    Evidence Unbiased microtubule-associated protein screen, knockout, ppMLC quantification, and myosin phosphatase activity assays in epithelial cells

    PMID:33346378

    Open questions at the time
    • How microtubules facilitate LUZP1's inhibition of myosin phosphatase not defined
    • Direct binding target within the phosphatase complex unidentified
  4. 2021 Medium

    Extended LUZP1's roles to actin polymerization control and chromatin remodeling, revealing context-specific functions beyond filament bundling.

    Evidence CRISPR knockout with migration/invasion, viability, centriole and ARP3/phospho-cofilin readouts; Co-IP/MS of the CERF complex in ES cells versus testis

    PMID:33869174 PMID:34197713

    Open questions at the time
    • CERF stabilization role inferred, not tested by mutagenesis
    • Functional significance of LUZP1 in chromatin remodeling not linked to a transcriptional output
  5. 2023 High

    Pinpointed a cytokinesis function by showing LUZP1 restrains contractile ring constriction via inhibition of DAPK3-mediated MYL9 phosphorylation.

    Evidence siRNA, time-lapse cytokinesis imaging, MS, Co-IP, CPC-inhibitor localization, and DAPK3-MYL9 kinase assay

    PMID:38009294

    Open questions at the time
    • How CPC activity and KIF20A direct LUZP1 localization mechanistically not resolved
    • Whether DAPK3 inhibition is direct competitive or allosteric not determined
  6. 2024 Medium

    Resolved the actomyosin-level mechanism by which LUZP1 organizes contractile bundles, showing it enables myosin II stack maturation and force generation.

    Evidence Knockout with live-cell myosin II filament imaging, traction force microscopy, and migration assays

    PMID:38832964

    Open questions at the time
    • Molecular step in myosin II concatenation directly bound or modified by LUZP1 not defined
    • Relationship to its phosphatase-inhibition role not integrated
  7. 2025 High

    Demonstrated a neuronal function distinct from earlier cytoskeletal roles, linking LUZP1 to dendritic spine maturation and behavior via filamin A and Rac1-PAK1.

    Evidence Conditional CaMKIIα-Cre knockout, shRNA, spine morphology, electrophysiology (LTP), Co-IP with filamin A, Rac1-PAK1 assays, and learning/memory tests

    PMID:40180573

    Open questions at the time
    • Whether filamin A binding and Rac1-PAK1 modulation are sequential or parallel not resolved
    • Connection to the centrosomal/ciliary actin functions in neurons not addressed
  8. 2026 Medium

    Established how LUZP1 levels are set and how its loss is pathogenic, showing COP1-mediated degradation and NF-κB induction control LUZP1 abundance with disease consequences.

    Evidence Ubiquitination and kinase assays, Co-IP, patient-derived organoid multi-omics in colorectal cancer; NF-κB inhibitor and IL-1β/TNF-α cytokine perturbation with migration rescue in HNSCC

    PMID:41937206 PMID:41952496

    Open questions at the time
    • COP1 recognition motif on LUZP1 not mapped
    • Whether NF-κB and COP1 act coordinately to set LUZP1 levels in the same context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LUZP1's many context-specific roles (centrosomal actin, tight junction, cytokinesis, neuronal, chromatin) are coordinated by a single protein remains unresolved.
  • No structural model defining how LUZP1 selects between actin, microtubule, and myosin partners
  • No unifying determinant of LUZP1 subcellular targeting across cell types

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1
Partners
ARP2CECR2COP1DAPK3EPLINFLNAMYL9SALL1
Complex memberships
CERF (CECR2-containing chromatin remodeling factor) complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 LUZP1 (LUZP) deficiency in knockout mice causes cranial neural tube closure defect (NTD) with ectopic Sonic Hedgehog expression and elevated apoptosis in the dorsal lateral neuroepithelium of the hindbrain, establishing a role for LUZP1 in neural tube closure during brain development. Knockout mouse (Luzp-KO/lacZ-KI), lacZ reporter expression, immunohistochemistry for Sonic Hedgehog, TUNEL assay for apoptosis Biochemical and biophysical research communications Medium 18801334
2020 LUZP1 localizes around centrioles and to actin cytoskeleton; loss of LUZP1 reduces F-actin levels, facilitates ciliogenesis, and alters Sonic Hedgehog signaling; truncated SALL1 (causative in Townes-Brocks Syndrome) increases ubiquitin proteasome-mediated degradation of LUZP1. LUZP1 was identified as an interactor of truncated SALL1 by TurboID proximity labeling and pulldowns, and associates with centrosome and actin filament factors. TurboID proximity labeling, pulldown assays, immunofluorescence localization, LUZP1 loss-of-function (siRNA/CRISPR), F-actin measurement, ciliogenesis assay, Sonic Hedgehog signaling reporter, ubiquitin-proteasome inhibitor rescue eLife High 32553112
2020 LUZP1 is an actin-stabilizing protein that localizes to actin filaments and the centrosome/basal body; its depletion increases MyosinVa at the centrosome and promotes primary cilia formation. LUZP1 regulates actin dynamics by mobilizing ARP2 to centrosomes and interacts with EPLIN as well as known ciliogenesis and cilia-length regulators. siRNA depletion, immunofluorescence localization, ciliogenesis assay, actin dynamics assays, co-immunoprecipitation/proximity labeling for LUZP1-EPLIN and ARP2 interactions, centrosome ARP2 recruitment assay The Journal of cell biology High 32496561
2020 LUZP1 is a microtubule-associated protein that localizes to tight junction (TJ)-associated circumferential actomyosin rings but not adherens junction rings. Di-phosphorylated myosin light chain (ppMLC) promotes LUZP1 recruitment to TJ-associated rings, where LUZP1 inhibits myosin phosphatase in a microtubule-facilitated manner, sustaining ppMLC levels and driving epithelial cell apical constriction. Unbiased screening of microtubule-associated proteins in AJC-enriched fraction, immunofluorescence localization, LUZP1 knockout, ppMLC quantification, myosin phosphatase activity assays, epistasis/rescue assays The EMBO journal High 33346378
2021 CRISPR/Cas9-mediated loss of Luzp1 in mouse fibroblasts promotes cell migration and invasion, reduces cell viability, increases apoptosis, increases centriole numbers and nuclear size, and alters ACTR3/ARP3 and phospho-cofilin ratios, implicating LUZP1 in the regulation of actin polymerization beyond filament bundling. CRISPR/Cas9 knockout, cell migration and invasion assays, viability/apoptosis assays, immunofluorescence for centriole number/nuclear size, Western blot for ARP3 and phospho-cofilin 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 (ES) cells but not in the testis, indicating tissue-specific complex composition. LUZP1 appears to stabilize the CERF complex in ES cells. Co-immunoprecipitation, mass spectrometry identification of CERF complex components in ES cells and testis 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, with these localizations regulated by CPC activity and KIF20A. LUZP1 interacts with DAPK3 (death-associated protein kinase 3) and MYL9 (myosin light chain 9), and inhibits MYL9 phosphorylation by DAPK3. Loss of LUZP1 accelerates contractile ring constriction velocity during cytokinesis. siRNA knockdown, time-lapse imaging of cytokinesis, mass spectrometry, co-immunoprecipitation, immunofluorescence localization, CPC inhibitor treatment, kinase activity assay for DAPK3-MYL9 phosphorylation The FEBS journal High 38009294
2024 LUZP1 plays a central role in the maturation of thick contractile actomyosin bundles; its knockout results in defective concatenation and persistent association of myosin II filaments, impairing myosin II stack assembly and thick ventral stress fiber formation, leading to abnormal cell morphogenesis, migration, and force generation. LUZP1 knockout, live-cell imaging of myosin II filament dynamics, immunofluorescence, traction force microscopy, cell morphology and migration assays Cellular and molecular life sciences Medium 38832964
2025 LUZP1 localizes to actin in CaMKIIα-expressing hippocampal dentate gyrus neurons; its depletion impedes dendritic spine maturation (excess filopodia, loss of mushroom spines) in vitro and in vivo, reduces spontaneous electrical activity and synaptic plasticity. Mechanistically, LUZP1 directly interacts with filamin A and modulates the Rac1-PAK1 signaling pathway to control dendritic maturation. Conditional deletion in CaMKIIα neurons impairs learning and memory. Conditional LUZP1 knockout (CaMKIIα-Cre), shRNA knockdown in vitro and in vivo, immunofluorescence localization, dendritic spine morphology analysis, electrophysiology (spontaneous activity, LTP), co-immunoprecipitation with filamin A, Rac1-PAK1 activity assay, behavioral learning/memory tests The Journal of neuroscience High 40180573
2026 The E3 ubiquitin ligase COP1 ubiquitinates and degrades LUZP1, thereby releasing DAPK3 from LUZP1-mediated suppression and leading to enhanced MYL9 phosphorylation, EMT activation, and JAK2-STAT3-CCND2 signaling, promoting colorectal cancer liver metastasis and oxaliplatin resistance. In vitro and in vivo functional experiments, multi-omics analysis of patient-derived organoids, ubiquitination assay, co-immunoprecipitation, kinase activity assay, EMT and signaling pathway readouts Experimental hematology & oncology Medium 41937206
2026 NF-κB acts as a key upstream transcriptional regulator of LUZP1 expression: NF-κB inhibition reduces LUZP1 levels, while stimulation with IL-1β or TNF-α induces LUZP1 upregulation and rescues migration defects caused by LUZP1 depletion in head and neck squamous cell carcinoma cells. NF-κB inhibitor treatment, cytokine stimulation (IL-1β, TNF-α), LUZP1 knockdown, migration/invasion assays, rescue experiment Oncology reports Medium 41952496

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 LUZP deficiency affects neural tube closure during brain development. Biochemical and biophysical research communications 36 18801334
2020 LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome. eLife 32 32553112
2020 LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation. The Journal of cell biology 29 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 14 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 12 34869035
2021 Chromatin remodeling factor CECR2 forms tissue-specific complexes with CCAR2 and LUZP1. Biochemistry and cell biology = Biochimie et biologie cellulaire 8 34197713
2022 LUZP1: A new player in the actin-microtubule cross-talk. European journal of cell biology 5 35738212
2024 LUZP1 regulates the maturation of contractile actomyosin bundles. Cellular and molecular life sciences : CMLS 3 38832964
2023 Leucine zipper protein 1 (LUZP1) regulates the constriction velocity of the contractile ring during cytokinesis. The FEBS journal 3 38009294
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

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