Affinage

CPAP

Centrosomal P4.1-associated protein · UniProt Q9HC77

Length
1338 aa
Mass
153.0 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

CPAP (CENPJ) is a cell-cycle-regulated centrosomal protein that governs centriole biogenesis, length control, and spindle pole integrity through its intrinsic tubulin-binding activities. Its PN2-3 domain forms a high-affinity complex with GTP-tubulin via a 'clutch-like' mechanism that delivers tubulin dimers to growing centriolar microtubules, thereby defining microtubule triplet number and centriole length, while an adjacent microtubule-destabilizing domain modulates local microtubule dynamics (PMID:27306797, PMID:18586240). CPAP protein levels are tightly controlled: PLK2 phosphorylation at S589/S595 promotes procentriole assembly, Aurora-A phosphorylation at S467 maintains pericentriolar material cohesion during mitosis, tankyrase 1-mediated PARsylation targets CPAP for proteasomal degradation in G1, and centrobin binding shields CPAP from ubiquitin-dependent destruction (PMID:20531387, PMID:26997271, PMID:22699936, PMID:25616662). Upstream factors Cep152 and WDR62 recruit CPAP to the centrosome, where it cooperates with STIL, CEP120, and hSAS6 to coordinate procentriole formation; loss-of-function mutations in CPAP cause autosomal recessive primary microcephaly (MCPH6), linked to defective centriole assembly, p53-dependent apoptosis of neural progenitors, and premature neuronal differentiation (PMID:21059844, PMID:22020124, PMID:23857771, PMID:32501282, PMID:35309908).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Identifying CPAP as a centrosomal component associated with γ-tubulin established it as a candidate microtubule-nucleation factor, opening the question of how it contributes to centrosome function.

    Evidence Yeast two-hybrid, co-IP, sucrose gradient co-sedimentation with γ-tubulin, and antibody inhibition of aster formation in human cells

    PMID:11003675

    Open questions at the time
    • Direct nucleation mechanism unclear
    • Relationship to centriole structure not addressed
    • Whether CPAP is a stoichiometric subunit of the γ-TuRC was not resolved
  2. 2005 Medium

    RNAi depletion revealed CPAP is essential for maintaining centrosome integrity during mitosis, with its loss causing multipolar spindles and mitotic arrest — shifting the model from nucleation accessory to structural centrosome component.

    Evidence siRNA knockdown in human cells combined with monastrol (Eg5 inhibitor) epistasis and immunofluorescence

    PMID:16316625

    Open questions at the time
    • Single-lab observation
    • Mechanism of centrosome fragmentation unknown
    • Whether phenotype reflects centriole vs. PCM defect not distinguished
  3. 2008 High

    Mapping a discrete microtubule-destabilizing domain (MDD) with defined catalytic residues adjacent to a microtubule-binding domain showed CPAP directly modulates microtubule dynamics, not just nucleation.

    Evidence In vitro MT destabilization assay with site-directed mutagenesis; conservation confirmed in Drosophila SAS-4

    PMID:18586240

    Open questions at the time
    • In vivo relevance of MDD activity not tested
    • How destabilization and stabilization activities are coordinated unknown
  4. 2009 High

    Gain- and loss-of-function studies demonstrated CPAP is a cell-cycle-regulated master regulator of centriole length: excess CPAP drives elongated procentriole-like structures, while CP110 antagonizes this elongation by capping distal ends.

    Evidence Overexpression/RNAi in human cells with electron microscopy and immunofluorescence; tubulin-binding-defective mutant (377EE) blocks elongation

    PMID:19481458 PMID:19503075

    Open questions at the time
    • Mechanism of cell-cycle-dependent CPAP degradation not identified
    • Structural basis of CP110–CPAP antagonism unknown
  5. 2009 Medium

    Discovery that CPAP homodimerizes via its fifth coiled-coil domain and that mitotic phosphorylation releases this interaction explained how CPAP maintains centrosome cohesion in interphase and permits splitting at mitosis entry.

    Evidence Co-IP with truncation mutants, cell-cycle synchronization, immunofluorescence

    PMID:19889632

    Open questions at the time
    • Kinase responsible for mitotic phosphorylation not identified at this stage
    • In vivo significance of dimerization not tested by point mutation
  6. 2010 High

    Identification of Cep152 as an upstream recruiter of CPAP and PLK2 as the kinase phosphorylating CPAP at S589/S595 for procentriole assembly placed CPAP within a defined signaling hierarchy for centriole duplication.

    Evidence Co-IP, RNAi epistasis for Cep152; in vitro kinase assay and phospho-resistant mutant analysis for PLK2

    PMID:20531387 PMID:21059844

    Open questions at the time
    • Direct structural basis of Cep152–CPAP interaction not resolved
    • Whether PLK2 and PLK4 phosphorylation events are sequential or redundant unclear
  7. 2011 High

    STIL was established as a direct CPAP-binding partner essential for procentriole formation; the MCPH-causing E1235V mutation in CPAP disrupts this interaction, providing the first direct link between a specific CPAP molecular defect and microcephaly.

    Evidence Co-IP, pulldown, RNAi epistasis, and disease-mutation functional analysis in human cells

    PMID:22020124 PMID:22100914

    Open questions at the time
    • Structural detail of CPAP–STIL interface unknown
    • How E1235V specifically perturbs brain development vs. other tissues not explained
  8. 2012 High

    Tankyrase 1-mediated PARsylation was shown to target CPAP for proteasomal degradation specifically in G1, solving the question of how CPAP levels are reset after mitosis to prevent centriole over-elongation.

    Evidence In vitro PARsylation reconstitution, overexpression/depletion of tankyrase 1, proteasome inhibition, cell-cycle analysis

    PMID:22699936

    Open questions at the time
    • E3 ubiquitin ligase linking PARsylation to proteasomal degradation not identified
    • Whether tankyrase 1 regulation is conserved in non-human species unknown
  9. 2013 High

    CEP120 was identified as a direct CPAP partner that cooperates through microtubule binding to regulate centriole elongation, expanding the elongation module beyond CPAP alone.

    Evidence Reciprocal Co-IP, bidirectional RNAi epistasis, MT-binding-defective mutant (CEP120-K76A)

    PMID:23857771

    Open questions at the time
    • Stoichiometry and order of CEP120–CPAP assembly on centrioles not defined
    • Whether CEP120 modulates CPAP tubulin-delivery activity directly is unknown
  10. 2015 High

    In vivo studies revealed CPAP's dual role in cortical development: centrosome biogenesis in radial glia progenitors and microtubule dynamics in migrating post-mitotic neurons, with centrobin identified as a stabilizer that protects CPAP from proteasomal degradation.

    Evidence In utero electroporation RNAi with rescue (Ascl1–CPAP axis); Co-IP and proteasome inhibition for centrobin–CPAP interaction

    PMID:25616662 PMID:25753651

    Open questions at the time
    • How centrobin shielding is relieved for timely CPAP turnover unknown
    • Relative contributions of CPAP to progenitor division vs. neuronal migration not quantified
  11. 2016 High

    Crystal structure of the PN2-3–tubulin complex defined a 'clutch-like' tubulin delivery mechanism: two structural elements engage GTP-tubulin, and tuning their affinity via mutagenesis either shortens or over-elongates centrioles, providing the first atomic-level model for centriole length control.

    Evidence X-ray crystallography, in vitro binding, site-directed mutagenesis (F375A, EE343RR), electron microscopy of centrioles

    PMID:27306797

    Open questions at the time
    • How the clutch mechanism is regulated in vivo by post-translational modifications not determined
    • Whether the mechanism applies to ciliary microtubule extension is untested
  12. 2016 High

    Aurora-A phosphorylation of CPAP at S467 was shown to maintain spindle pole integrity by switching CPAP from microtubule binding to PCM recruitment, revealing how CPAP function is remodeled during mitosis.

    Evidence In vitro kinase assay, phospho-mimic/resistant mutagenesis rescue, immunofluorescence

    PMID:26997271

    Open questions at the time
    • Structural basis for phosphorylation-induced affinity switch not resolved
    • Whether Aurora-A targets CPAP at the same time as the dimerization-release event is unclear
  13. 2018 High

    Pharmacological disruption of the CPAP–tubulin interface (CCB02) validated the model that tubulin binding restrains PCM-dependent microtubule nucleation, offering a potential therapeutic strategy for cancers with centrosome amplification.

    Evidence Small-molecule screening, in vitro binding, genetic perturbation, 3D cancer cell models

    PMID:30530478

    Open questions at the time
    • Selectivity and off-target profile of CCB02 in vivo not fully characterized
    • Whether the strategy is effective in primary tumors beyond cell lines unknown
  14. 2019 Medium

    A non-canonical nuclear function was uncovered: CPAP directly binds STAT3 and acts as a transcriptional co-activator promoting IL-6/STAT3-driven tumor growth and angiogenesis, extending CPAP's roles beyond centrosome biology.

    Evidence Co-IP, siRNA knockdown, luciferase reporter, in vivo xenograft tumor models in hepatocellular carcinoma

    PMID:31511651

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Mechanism by which a centrosomal protein accesses nuclear STAT3 targets not explained
    • Whether the STAT3 co-activator function is separable from centrosome roles unknown
  15. 2020 High

    Conditional knockout in mouse brain confirmed CPAP is essential for centriole/cilium biogenesis in radial glia; apoptosis of progenitors is p53-dependent, and WDR62 was placed upstream of CPAP in a ciliogenesis pathway controlling neocortical development.

    Evidence Cre-lox conditional knockout with p53 co-deletion rescue; CRISPR knock-in WDR62 mutant mice with CPAP localization analysis

    PMID:31816041 PMID:32501282

    Open questions at the time
    • Whether p53 activation is via the mitotic surveillance pathway or DNA damage not distinguished
    • How WDR62 physically recruits CPAP is structurally unresolved
  16. 2022 High

    Human iPSC-derived brain organoids carrying the MCPH-causing E1235V mutation showed that CPAP is required for proper centriolar recruitment of elongation factors (CEP120, CEP295, centrobin, POC5, POC1B), directly linking the molecular defect to short centrioles, aberrant ciliogenesis, and microcephaly-like organoid phenotypes.

    Evidence CRISPR-Cas9 isogenic hiPSC lines, brain organoid culture, proximity ligation assay, immunofluorescence

    PMID:35309908

    Open questions at the time
    • Whether the E1235V defect is rescuable by restoring STIL interaction alone is untested
    • Long-range cortical circuitry effects not modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the CPAP–STIL and CPAP–Cep152 interfaces, how multiple phosphorylation events (PLK2, Aurora-A, mitotic phosphorylation of coiled-coil domain) are temporally coordinated during the centrosome cycle, whether the STAT3 co-activator function is physiologically significant outside hepatocellular carcinoma, and the identity of the E3 ligase linking tankyrase 1-mediated PARsylation to CPAP ubiquitination.
  • No structural model for CPAP–STIL or CPAP–Cep152 complexes
  • Temporal integration of PLK2, Aurora-A, and tankyrase 1 regulation not mapped
  • STAT3 co-activator role awaits independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0140110 transcription regulator activity 1
Localization
GO:0005815 microtubule organizing center 8 GO:0005634 nucleus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 7 R-HSA-1640170 Cell Cycle 6 R-HSA-1266738 Developmental Biology 4 R-HSA-5357801 Programmed Cell Death 2
Complex memberships
γ-tubulin complex (co-sedimentation)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CPAP (centrosomal P4.1-associated protein) was identified as a novel centrosomal protein that interacts with the head domain of protein 4.1R-135 (via yeast two-hybrid), co-sediments and co-immunoprecipitates with gamma-tubulin, indicating it is part of the gamma-tubulin complex, and localizes within the center of microtubule asters; anti-CPAP antibody significantly inhibited microtubule aster formation, suggesting CPAP participates in microtubule nucleation. Yeast two-hybrid, co-immunoprecipitation, sucrose gradient sedimentation, immunofluorescence, antibody inhibition assay Molecular and cellular biology High 11003675
2005 Depletion of CPAP by RNAi arrested cells in mitosis and induced apoptosis, with >40% of mitotic cells showing multiple spindle poles; inhibition of kinesin Eg5 in CPAP-depleted cells resulted in monopolar spindles, demonstrating that Eg5 is required for multipolar spindle formation in the absence of CPAP and revealing a structural role for CPAP in maintaining centrosome integrity and normal spindle morphology during cell division. siRNA knockdown, inhibitor (monastrol) treatment, immunofluorescence microscopy Biochemical and biophysical research communications Medium 16316625
2008 CPAP contains a microtubule-destabilizing domain (MDD; residues 311–422) adjacent to a microtubule-binding domain (MBD; residues 423–607); site-specific mutagenesis of the MDD (Y341P, I346P, L348P, triple-P, KR377EE) abolished microtubule-destabilizing activity and tubulin-dimer binding; conserved sequence in Drosophila d-SAS-4 similarly mediates MT destabilization, suggesting functional conservation. In vitro microtubule destabilization assay, site-directed mutagenesis, truncation analysis, tubulin-binding assay Experimental cell research High 18586240
2009 CPAP expression is cell-cycle regulated, with the protein being degraded in late mitosis. Depletion of CPAP inhibited centrosome duplication, whereas excess CPAP induced formation of elongated procentriole-like structures (PLSs) containing stable microtubules and centriolar proteins. A tubulin-dimer binding-defective CPAP mutant (CPAP-377EE) significantly inhibited PLS formation, demonstrating that CPAP's intrinsic tubulin-dimer binding activity is required for procentriole elongation. RNAi depletion, overexpression, site-directed mutagenesis, immunofluorescence, ultrastructural analysis Nature cell biology High 19503075
2009 Overexpression of CPAP in human cells leads to accumulation of centriolar tubulin and dramatically elongated centrioles. CP110 (a distal end-capping protein) and CPAP play antagonistic roles: CPAP promotes tubulin addition and centriole elongation, while CP110 caps the distal end to limit elongation. Loss of CP110 also produces elongated MT structures that differ from genuine primary cilia. Overexpression, RNAi depletion, immunofluorescence, electron microscopy Current biology : CB High 19481458
2009 CPAP forms a homodimer during interphase via its fifth coiled-coil domain; this self-interaction is required for maintaining centrosome cohesion and preventing premature centrosome splitting before G2/M. CPAP is phosphorylated during mitosis, and this phosphorylation releases the intermolecular interaction, orchestrating centrosome splitting and ensuring genomic stability. Co-immunoprecipitation, domain-mapping with truncation mutants, cell cycle analysis, immunofluorescence The Journal of biological chemistry Medium 19889632
2010 Cep152 interacts with CPAP and recruits it to the centrosome; reduction of Cep152 causes loss of centrioles and failure of centriole duplication and prevents recruitment of both Plk4 and CPAP to the centrosome, placing Cep152 upstream of CPAP in the centriole biogenesis pathway. Co-immunoprecipitation, RNAi depletion, immunofluorescence, epistasis analysis The Journal of cell biology High 21059844
2010 PLK2 phosphorylates CPAP at S589 and S595 in vitro and in vivo; this phosphorylation is critical for procentriole formation and centriole elongation during the centrosome cycle. Phosphorylated CPAP is preferentially located at the procentriole. Overexpression of a phospho-resistant CPAP mutant failed to support elongated centriole formation. PLK4 also phosphorylates S595 but is not a critical step in PLK4-driven procentriole assembly. In vitro kinase assay, phospho-specific antibody, overexpression of phospho-resistant mutant, immunofluorescence The EMBO journal High 20531387
2011 STIL directly interacts with CPAP and forms a complex with hSAS6; a natural MCPH-causing CPAP mutation (E1235V) significantly reduces CPAP binding to STIL. STIL is required for procentriole formation and for localization of hSAS6 and CPAP to the base of nascent procentrioles; STIL depletion inhibits CPAP-induced centriole elongation, placing STIL and CPAP in a shared pathway for centriole biogenesis. Co-immunoprecipitation, pulldown, RNAi depletion, overexpression, immunofluorescence, disease-mutation analysis The EMBO journal High 22020124
2011 CPAP protein domains required for centriolar localization and for centriole elongation and formation were identified; conditions mimicking CPAP MCPH patient mutations compromise centriole formation in tissue culture cells and correlate with randomization of spindle position as shown using adhesive micropatterns. STIL was also found essential for centriole formation and proper spindle positioning. Domain deletion analysis, overexpression, RNAi depletion, adhesive micropatterning, immunofluorescence Journal of cell science Medium 22100914
2012 Tankyrase 1 PARsylates CPAP in vitro and in vivo; overexpression of tankyrase 1 leads to proteasomal degradation of CPAP, preventing centriole duplication, whereas depletion of tankyrase 1 stabilizes CPAP in G1 and generates elongated procentrioles and multipolarity. Tankyrase 1 localizes to centrosomes exclusively in G1, coinciding with CPAP degradation, establishing tankyrase 1-mediated PARsylation as a mechanism controlling CPAP levels to limit centriole elongation. In vitro PARsylation assay, overexpression/depletion, proteasome inhibition, immunofluorescence, cell cycle analysis EMBO reports High 22699936
2013 CEP120 directly interacts with CPAP and is required for centriole duplication and elongation; CEP120 contains an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. Depletion of CEP120 inhibits CPAP-induced centriole elongation and vice versa; a microtubule binding-defective CEP120-K76A mutant suppressed elongated centriole formation, indicating CEP120 and CPAP cooperate through microtubule binding to regulate centriole elongation. Co-immunoprecipitation, RNAi depletion, overexpression, site-directed mutagenesis, immunofluorescence The Journal of cell biology High 23857771
2015 CPAP is a transcriptional target of the proneural factor Ascl1 in the embryonic cerebral cortex. In utero electroporation knockdown of Cenpj/CPAP disrupts centrosome biogenesis, randomizes cleavage plane orientation of radial glia progenitors, increases stable microtubules in post-mitotic neurons causing slower neuronal migration and aberrant centrosome positioning. Rescue experiments confirmed that Cenpj mediates Ascl1's role in centrosome biogenesis and microtubule dynamics. In utero electroporation RNAi, luciferase reporter assay, immunofluorescence, rescue experiments Nature communications High 25753651
2015 Centrobin interacts with CPAP and prevents its proteasomal degradation; centrobin depletion renders CPAP undetectable via ubiquitin/proteasome-mediated degradation, while reintroduction of full-length centrobin (but not a CPAP-binding-defective mutant) restored CPAP levels. Centrobin overexpression caused proteasome-independent accumulation of ubiquitinated CPAP and abnormal elongated centrioles. Co-immunoprecipitation, RNAi depletion, proteasome inhibition, site-directed mutagenesis, immunofluorescence The Journal of biological chemistry High 25616662
2016 The PN2-3 domain of CPAP binds tubulin via two distinct structural elements: a C-terminal loop-helix targeting β-tubulin at the microtubule outer surface, and an N-terminal helical motif capping the α-β surface of β-tubulin. PN2-3 forms a high-affinity complex with GTP-tubulin, which is crucial for defining numbers and lengths of centriolar/ciliary microtubules. CPAP(F375A) with strongly reduced tubulin interaction causes shorter centrioles exhibiting doublet- instead of triplet-microtubules, while CPAP(EE343RR) induces over-elongation by enhanced dynamic release of bound tubulin ('clutch-like' mechanism). Crystal structure, in vitro binding assay, site-directed mutagenesis, functional overexpression/rescue, electron microscopy Nature communications High 27306797
2016 Aurora-A directly interacts with and phosphorylates CPAP at serine 467 during mitosis. This phosphorylation is required for maintenance of spindle pole integrity: depletion of CPAP or expression of non-phosphorylatable CPAP-S467A caused PCM dispersion and multipolar mitotic abnormalities, while phospho-mimic CPAP-S467D rescued PCM integrity. CPAP-S467D showed low microtubule-binding affinity but high affinity for PCM proteins. In vitro kinase assay, phospho-specific antibody, site-directed mutagenesis (phospho-mimic/resistant), immunofluorescence, Co-immunoprecipitation Cell reports High 26997271
2018 Tubulin interaction with CPAP negatively regulates CPAP-dependent pericentriolar material (PCM) recruitment and microtubule nucleation. A small molecule, CCB02, was identified that selectively binds the CPAP-binding site of tubulin. Genetic and chemical perturbation of CPAP-tubulin interaction activates extra centrosomes to nucleate enhanced numbers of microtubules, causing centrosome de-clustering, multipolar mitosis, and cell death in cancer cells with centrosome amplification. Small-molecule screening, in vitro binding assay, genetic perturbation, 3D-organotypic invasion assay, immunofluorescence The EMBO journal High 30530478
2019 CPAP acts as a transcriptional coactivator of STAT3 by directly binding STAT3; CPAP overexpression increases tumor growth, angiogenesis, and metastasis in hepatocellular carcinoma. Interrupting the CPAP-STAT3 interaction attenuates STAT3-mediated tumor growth and angiogenesis. CPAP knockdown impairs IL-6-mediated STAT3 activation, target gene expression (IL-8, CD44), cell migration, and invasion. Co-immunoprecipitation, siRNA knockdown, overexpression, luciferase reporter assay, in vivo tumor models Cell death and differentiation Medium 31511651
2020 Conditional knockout of Cpap in the mouse central nervous system preferentially induces monopolar spindles in radial glia progenitors, causes robust p53-dependent apoptosis disrupting embryonic brain development, and leads to cilia loss, RGP mislocalization, junctional integrity disruption, and severe cerebellar hypoplasia. Simultaneous removal of p53 rescues RGP death, indicating CPAP-loss-driven apoptosis is p53-dependent. Conditional knockout (Cre-lox), genetic epistasis (p53 co-deletion), immunofluorescence, histology Journal of cell science High 32501282
2020 WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP; as a consequence, recruitment of IFT88 (required for cilia formation) is deficient, leading to premature differentiation of radial glia and cortical thinning, placing WDR62 upstream of CPAP in a pathway controlling ciliogenesis and neocortical development. CRISPR/Cas9 knock-in mice, immunofluorescence co-localization, protein interaction analysis, histology Human molecular genetics Medium 31816041
2022 The MCPH-associated CPAP-E1235V mutant perturbs recruitment of centriolar elongation proteins (CEP120, CEP295, CENTROBIN, POC5, POC1B) onto nascent centrioles, producing short centrioles but long cilia. hiPSC-CPAP-E1235V-derived brain organoids exhibit p53-dependent neuronal cell death, altered spindle orientation of neuronal progenitor cells, and premature neuronal differentiation, resulting in smaller organoids that mimic microcephaly. CRISPR-Cas9 genome editing, hiPSC-derived brain organoids, immunofluorescence, proximity ligation assay Frontiers in cell and developmental biology High 35309908

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes & development 563 2253878
2014 CPAP, weight loss, or both for obstructive sleep apnea. The New England journal of medicine 366 24918371
1993 Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain. Nature 332 8336793
2009 Control of centriole length by CPAP and CP110. Current biology : CB 281 19481458
2009 CPAP is a cell-cycle regulated protein that controls centriole length. Nature cell biology 233 19503075
2010 Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. The Journal of cell biology 230 21059844
2011 The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. The EMBO journal 204 22020124
1997 CREB controls LAP/C/EBP beta transcription. Molecular and cellular biology 175 9199295
2000 Protein 4.1 R-135 interacts with a novel centrosomal protein (CPAP) which is associated with the gamma-tubulin complex. Molecular and cellular biology 143 11003675
2002 Changes in comorbidities and improvements in quality of life after LAP-BAND placement. American journal of surgery 141 12527352
1995 The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. Proceedings of the National Academy of Sciences of the United States of America 137 7568208
1994 LAP (NF-IL-6), a tissue-specific transcriptional activator, is an inhibitor of hepatoma cell proliferation. The EMBO journal 125 7906646
2016 Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis. The Journal of allergy and clinical immunology 116 27417020
2013 Membrane-bound RLCKs LIP1 and LIP2 are essential male factors controlling male-female attraction in Arabidopsis. Current biology : CB 108 23684977
2003 The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of CD4. Journal of virology 106 12502858
2003 Lap-band: outcomes and results. Journal of laparoendoscopic & advanced surgical techniques. Part A 106 14561255
1999 Plastid translation is required for the expression of nuclear photosynthesis genes in the dark and in roots of the pea lip1 mutant. The Plant cell 104 10330474
2007 Isolation and expression of a Malassezia globosa lipase gene, LIP1. The Journal of investigative dermatology 100 17460728
2013 CEP120 interacts with CPAP and positively regulates centriole elongation. The Journal of cell biology 99 23857771
2011 Spindle positioning in human cells relies on proper centriole formation and on the microcephaly proteins CPAP and STIL. Journal of cell science 95 22100914
2008 Selective effects of CPAP on sleep apnoea-associated manifestations. European journal of clinical investigation 92 18627419
2006 Convergent and divergent ligand specificity among PDZ domains of the LAP and zonula occludens (ZO) families. The Journal of biological chemistry 92 16737968
2013 Integrating psychology and medicine in CPAP adherence--new concepts? Sleep medicine reviews 83 23725820
1998 Design, total synthesis, and functional overexpression of the Candida rugosa lip1 gene coding for a major industrial lipase. Protein science : a publication of the Protein Society 81 9655346
2015 Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP. Oncotarget 78 26343373
1992 Regulated expression of alpha 2,6-sialyltransferase by the liver-enriched transcription factors HNF-1, DBP, and LAP. The Journal of biological chemistry 75 1737800
2001 LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Human molecular genetics 73 11741830
2002 Integrin alpha8beta1 mediates adhesion to LAP-TGFbeta1. Journal of cell science 72 12415008
1997 Cloning and characterization of a gene (LIP1) which encodes a lipase from the pathogenic yeast Candida albicans. Microbiology (Reading, England) 70 9043110
2012 Influence of CPAP treatment on airway and systemic inflammation in OSAS patients. Sleep & breathing = Schlaf & Atmung 69 22945540
2002 Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses. Virus research 68 12297327
2009 Expression of LAP, a SecA2-dependent secretory protein, is induced under anaerobic environment. Microbes and infection 64 19454322
2016 Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length. Nature communications 63 27306797
2008 Functional characterization of the microtubule-binding and -destabilizing domains of CPAP and d-SAS-4. Experimental cell research 61 18586240
2007 Female inheritance of malarial lap genes is essential for mosquito transmission. PLoS pathogens 60 17335349
2004 C/EBP beta isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver. Hepatology (Baltimore, Md.) 59 15368440
2018 PDL2+ CD11b+ dermal dendritic cells capture topical antigen through hair follicles to prime LAP+ Tregs. Nature communications 58 30531969
2011 Inducible CD4+LAP+Foxp3- regulatory T cells suppress allergic inflammation. Journal of immunology (Baltimore, Md. : 1950) 58 22079987
2010 PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. The EMBO journal 57 20531387
2020 From Input to Output: The Lap/c-di-GMP Biofilm Regulatory Circuit. Annual review of microbiology 56 32689917
2001 Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells. The Journal of biological chemistry 54 11440998
2012 Tankyrase 1 regulates centrosome function by controlling CPAP stability. EMBO reports 52 22699936
2011 CD39+ regulatory T cells suppress generation and differentiation of Th17 cells in human malignant pleural effusion via a LAP-dependent mechanism. Respiratory research 51 21663645
2017 Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells. Nature communications 50 28928467
2004 Reactivity of pure Candida rugosa lipase isoenzymes (Lip1, Lip2, and Lip3) in aqueous and organic media. influence of the isoenzymatic profile on the lipase performance in organic media. Biotechnology progress 50 14763825
2005 Depletion of CPAP by RNAi disrupts centrosome integrity and induces multipolar spindles. Biochemical and biophysical research communications 49 16316625
2015 Cenpj/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1. Nature communications 47 25753651
1997 Characterization of the chromatin binding activity of lamina-associated polypeptide (LAP) 2. Biochemical and biophysical research communications 46 9299486
2019 CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity. Cell death and differentiation 45 31511651
2014 Lamina-associated polypeptide (LAP)2α and other LEM proteins in cancer biology. Advances in experimental medicine and biology 45 24563347
2007 Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome. American journal of physiology. Regulatory, integrative and comparative physiology 44 17634199
2018 SPOC domain-containing protein Leaf inclination3 interacts with LIP1 to regulate rice leaf inclination through auxin signaling. PLoS genetics 43 30496185
2013 Role of C/EBPβ-LAP and C/EBPβ-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes. Differentiation; research in biological diversity 42 23314288
2008 The cold-active Lip1 lipase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 is a member of a new bacterial lipolytic enzyme family. Extremophiles : life under extreme conditions 42 18437283
2020 LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness. Frontiers in oncology 39 32850405
2016 Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP) Cells. Journal of thyroid research 38 27057371
2002 The tyrosine motifs of Lamp 1 and LAP determine their direct and indirect targetting to lysosomes. Journal of cell science 38 11801736
2015 Rubicon swaps autophagy for LAP. Nature cell biology 36 26123110
2007 Arabidopsis thaliana circadian clock is regulated by the small GTPase LIP1. Current biology : CB 36 17683937
2020 The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development. Human molecular genetics 35 31816041
2017 Yes1 signaling mediates the resistance to Trastuzumab/Lap atinib in breast cancer. PloS one 35 28158234
2016 Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients. Oncotarget 34 26885615
2016 Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease. Autophagy 34 27028978
2024 CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization. EBioMedicine 33 38403558
2009 In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein. International journal of oncology 33 19724919
2001 Reverse transcription slippage over the mRNA secondary structure of the LIP1 gene. BioTechniques 32 11768657
2014 Impact of CPAP on activity patterns and diet in patients with obstructive sleep apnea (OSA). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 31 24910546
2005 A secreted lipase encoded by LIP1 is necessary for efficient use of saturated triglyceride lipids in Fusarium graminearum. Microbiology (Reading, England) 30 16339936
2020 Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue. Sleep 28 31872261
2020 Loss of CPAP in developing mouse brain and its functional implication for human primary microcephaly. Journal of cell science 28 32501282
2019 Oxidative stress and inflammatory profiles in obstructive sleep apnea: are short-term CPAP or aerobic exercise therapies effective? Sleep & breathing = Schlaf & Atmung 28 31313021
1990 Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP-35). International journal of cell cloning 27 2177080
2015 Overexpression of Candida rugosa lipase Lip1 via combined strategies in Pichia pastoris. Enzyme and microbial technology 26 26672457
2014 Targeted therapy for renal cell carcinoma: The next lap. Journal of carcinogenesis 26 24737951
2024 The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis. Molecular cancer 25 38664722
2015 Centrobin-mediated regulation of the centrosomal protein 4.1-associated protein (CPAP) level limits centriole length during elongation stage. The Journal of biological chemistry 25 25616662
2015 Of LAP, CUPS, and DRibbles - Unconventional Use of Autophagy Proteins for MHC Restricted Antigen Presentation. Frontiers in immunology 25 25972871
2015 Effect of Nasal CPAP on SIRT1 and Endothelial Function in Obstructive Sleep Apnea Syndrome. Lung 25 26345325
2011 Effect of CPAP on oxidative stress and circulating progenitor cell levels in sleep patients with apnea-hypopnea syndrome. Respiratory care 24 21605479
2019 Compliance after switching from CPAP to bilevel for patients with non-compliant OSA: big data analysis. BMJ open respiratory research 23 31178999
2018 Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells. The EMBO journal 23 30530478
2016 Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis. Cell reports 23 26997271
2022 Modeling Human Primary Microcephaly With hiPSC-Derived Brain Organoids Carrying CPAP-E1235V Disease-Associated Mutant Protein. Frontiers in cell and developmental biology 22 35309908
2013 Secreted Listeria adhesion protein (Lap) influences Lap-mediated Listeria monocytogenes paracellular translocation through epithelial barrier. Gut pathogens 22 23799938
2022 Characterization of Polymer Degrading Lipases, LIP1 and LIP2 From Pseudomonas chlororaphis PA23. Frontiers in bioengineering and biotechnology 21 35519608
2023 Precisely Constructing Renal-Clearable and LAP-Activatable Ratiometric Molecular Probes for Early Diagnosis of Acute and Chronic Kidney Injury Via Optimizing Asymmetric DPP Dyes. Analytical chemistry 20 38131222
2021 MERTK-Mediated LC3-Associated Phagocytosis (LAP) of Apoptotic Substrates in Blood-Separated Tissues: Retina, Testis, Ovarian Follicles. Cells 20 34207717
2019 LAP-like non-canonical autophagy and evolution of endocytic vacuoles in pancreatic acinar cells. Autophagy 20 31651224
2015 Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy. Journal of leukocyte biology 20 25722319
2012 Regulation of adipocyte 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) by CCAAT/enhancer-binding protein (C/EBP) β isoforms, LIP and LAP. PloS one 20 22662254
2021 A 3D-printed microfluidic platform for simulating the effects of CPAP on the nasal epithelium. Biofabrication 19 33561837
2023 Zebrafish Larvae Position Tracker (Z-LaP Tracker): a high-throughput deep-learning behavioral approach for the identification of calcineurin pathway-modulating drugs using zebrafish larvae. Scientific reports 18 36823315
2019 Effect of pembrolizumab on CD4+ CD25+ , CD4+ LAP+ and CD4+ TIM-3+ T cell subsets. Clinical and experimental immunology 18 30693485
2016 Effects of nasal CPAP on exhaled SIRT1 and tumor necrosis factor-α in patients with obstructive sleep apnea. Respiratory physiology & neurobiology 18 26976689
2015 Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity. Journal of Crohn's & colitis 18 26589955
2021 The Assessment of Endothelial Dysfunction among OSA Patients after CPAP Treatment. Medicina (Kaunas, Lithuania) 17 33806108
2018 Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics. Mediators of inflammation 17 29692681
2014 Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice. Atherosclerosis 17 25544178
2009 Dimerization of CPAP orchestrates centrosome cohesion plasticity. The Journal of biological chemistry 17 19889632
2021 Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy. ACS applied materials & interfaces 16 34894664