Affinage

CEP131

Centrosomal protein of 131 kDa · UniProt Q9UPN4

Length
1083 aa
Mass
122.1 kDa
Annotated
2026-04-28
25 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP131 (AZI1) is a centriolar satellite protein that functions as a microtubule-dependent trafficking factor essential for ciliogenesis, flagellogenesis, and centriolar satellite integrity. CEP131 is recruited to centriolar satellites by PCM1 and anchored at the centriolar core by pericentrin and Cep290; it traffics along microtubules via dynein-dynactin to the basal body and transition zone, where it cooperates with Cep162 to maintain Cep290 and initiate ciliogenesis (PMID:22797915, PMID:24415959, PMID:38442096). CEP131 regulates BBSome ciliary entry through direct interaction with BBS4, acting as a gatekeeper that restrains BBSome accumulation in cilia (PMID:24550735). Its satellite residency is dynamically controlled by phosphorylation at Ser-78 by both MK2 (stress-induced, creating 14-3-3 binding sites that sequester CEP131 cytoplasmically and disperse satellites) and PLK4 (maintaining satellite structural integrity under basal conditions) (PMID:26616734, PMID:30804208).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 Medium

    Initial characterization placed CEP131 in the male germline, establishing its expression in spermatogenesis and localization to the preacrosome region of spermatids, but its molecular function was unknown.

    Evidence Immunolocalization and RT-PCR in mouse spermatids and fibroblasts

    PMID:9070930

    Open questions at the time
    • No functional data beyond localization
    • Mechanism of preacrosomal targeting unknown
    • No connection to centrosomes or cilia yet recognized
  2. 2009 Medium

    Zebrafish knockdown revealed that CEP131 is required for proper cilia length and axoneme formation across multiple tissues, establishing it as a ciliary gene rather than merely a spermatogenesis factor.

    Evidence Morpholino knockdown in zebrafish embryos with ciliary imaging and laterality phenotyping

    PMID:19254375

    Open questions at the time
    • Morpholino-only approach without genetic confirmation
    • Molecular mechanism of cilia shortening not defined
    • Whether CEP131 acts cell-autonomously was untested
  3. 2011 High

    The Drosophila ortholog Dilatory was shown to localize to the basal body and transition zone and to be required for ciliogenesis and sperm motility, establishing an evolutionarily conserved role at the ciliary base and a genetic link to intraflagellar transport.

    Evidence Drosophila loss-of-function mutants with immunolocalization and genetic epistasis with Uncoordinated

    PMID:21750193

    Open questions at the time
    • Direct biochemical partners at the ciliary base not identified
    • Mechanism of IFT regulation unresolved
  4. 2012 High

    CEP131 was placed within the centriolar satellite protein network: PCM1 recruits it to satellites, pericentrin and Cep290 anchor it at the centriolar core, and its transport requires microtubules and dynein-dynactin, establishing a mechanistic framework for its satellite-dependent functions.

    Evidence siRNA knockdown, immunofluorescence, co-localization, and cell-cycle analysis in human cells

    PMID:22797915

    Open questions at the time
    • Direct physical interactions among PCM1/pericentrin/Cep290 and CEP131 not biochemically demonstrated
    • Precise cell-cycle signals regulating CEP131 localization unknown
  5. 2013 High

    Live imaging and a null mouse demonstrated that CEP131 traffics along microtubules to the basal body, is required for efficient ciliogenesis (rescued by siRNA-resistant construct), and is essential for spermatid manchette and flagella formation, unifying its roles in cilia and male fertility.

    Evidence siRNA knockdown with genetic rescue in mouse fibroblasts; gene-trap null mouse phenotyping

    PMID:24415959

    Open questions at the time
    • Cargo carried by CEP131 during microtubule-based trafficking not identified
    • Whether ciliogenesis defect is indirect via satellite disruption versus direct at the basal body undetermined
  6. 2014 High

    CEP131 was identified as a BBSome regulator through direct binding to BBS4, revealing it restrains BBSome ciliary entry and acts as a negative regulator of BBS-dependent ciliary trafficking.

    Evidence Reciprocal co-immunoprecipitation, siRNA epistasis in mammalian cells, zebrafish morpholino knockdown

    PMID:24550735

    Open questions at the time
    • Structural basis of CEP131-BBS4 interaction undefined
    • Whether CEP131 regulates other ciliary trafficking complexes beyond the BBSome untested
  7. 2015 High

    The p38-MK2 stress kinase pathway was shown to directly phosphorylate CEP131 at S47 and S78, creating 14-3-3 binding sites that sequester CEP131 in the cytoplasm and disperse centriolar satellites, establishing the first signaling mechanism controlling satellite dynamics through CEP131.

    Evidence In vitro kinase assay, phospho-site mutagenesis, co-IP with 14-3-3, UV stress in human cells

    PMID:26616734

    Open questions at the time
    • Whether 14-3-3 sequestration affects ciliogenesis under stress not tested
    • Additional phosphorylation sites and kinases potentially involved
  8. 2019 High

    PLK4 was identified as a second kinase phosphorylating CEP131 at Ser-78 under basal conditions, with this modification being essential for centriolar satellite structural integrity but dispensable for ciliogenesis and centriole duplication, revealing that the same phosphosite is read differently depending on kinase context.

    Evidence Analog-sensitive PLK4 phosphoproteomics, in vitro kinase assay, phospho-site mutagenesis in RPE-1 cells

    PMID:30804208

    Open questions at the time
    • How cells distinguish MK2-mediated vs PLK4-mediated phosphorylation at the same site is unresolved
    • Downstream effectors of satellite integrity maintenance unknown
  9. 2022 Medium

    A non-centrosomal function was reported: CEP131 interacts with ARID3A to co-occupy the KDM3A promoter and transcriptionally activate a histone demethylase cascade in liver cancer cells, suggesting CEP131 has nuclear roles beyond its satellite function.

    Evidence Co-immunoprecipitation, ChIP assay, gain/loss-of-function in hepatocellular carcinoma cells and xenografts

    PMID:36008383

    Open questions at the time
    • Nuclear localization of endogenous CEP131 not independently confirmed
    • Whether transcriptional role is widespread or cancer-specific is unknown
    • Single study without replication
  10. 2024 Medium

    Drosophila genetics revealed that CEP131 forms a cooperative module with Cep162 that, together with the Cby-Fam92 module, maintains Cep290 at the basal body to initiate ciliogenesis, placing CEP131 in a defined epistatic hierarchy for ciliogenesis initiation.

    Evidence Drosophila double-mutant genetics, immunolocalization, epistasis analysis

    PMID:38442096

    Open questions at the time
    • Direct physical interaction between CEP131 and Cep162 not biochemically demonstrated
    • Whether this modular architecture is conserved in mammals untested
    • Single study in Drosophila

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of cargoes transported by CEP131 along microtubules to the basal body, the structural basis of its interactions with BBS4 and satellite components, and whether its reported nuclear/transcriptional functions represent a bona fide second role or an overexpression artifact.
  • No cargo identified for CEP131 microtubule-based trafficking
  • No structural model of CEP131 or its complexes
  • Nuclear role lacks independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005815 microtubule organizing center 4 GO:0005929 cilium 3 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-1640170 Cell Cycle 1
Partners
ARID3ABBS4CEP162CEP290PCM1YWHAB
Complex memberships
centriolar satellites

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 CEP131/AZI1 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Depletion of Cep131 results in reduced proliferation, centriole amplification, increased multipolar mitosis, chromosomal instability, and post-mitotic DNA damage. siRNA knockdown, immunofluorescence, co-localisation studies, cell-cycle analysis Journal of cell science High 22797915
2013 Azi1/Cep131 localises to centriolar satellites and traffics along microtubules to become enriched around the basal body; it also localises to the transition zone. Acute siRNA knockdown in mouse fibroblasts causes robust reduction in ciliogenesis, rescued by siRNA-resistant Azi1-GFP. In Azi1 null mice, spermatid manchette and flagella show microtubule-based trafficking defects leading to male infertility, demonstrating a conserved non-essential trafficking role in ciliogenesis and an essential role in flagellogenesis. siRNA knockdown, live imaging/localisation, gene-trap null mouse, rescue with siRNA-resistant GFP fusion PLoS genetics High 24415959
2009 Cep131 depletion in zebrafish embryos results in shortened cilia in multiple tissues, kidney and ear developmental defects, and randomised left-right asymmetry, phenocopying intraflagellar transport mutants; centrosomes and basal bodies remain present, indicating Cep131 contributes to cilia length/axoneme formation. Morpholino knockdown in zebrafish embryos, ciliary imaging, phenotypic analysis BMC cell biology Medium 19254375
2011 The Drosophila CEP131 ortholog Dilatory (DILA) localises to the ciliary base including basal body and transition zone, is required for ciliogenesis in sensory neurons and sperm, and genetically interacts with the ciliary coiled-coil protein Uncoordinated, implicating it in regulating intraflagellar transport at the ciliary base. Drosophila loss-of-function mutants, immunolocalisation, genetic epistasis with Uncoordinated Journal of cell science High 21750193
2014 AZI1/CEP131 interacts with the BBSome through direct binding to BBS4. AZI1 is not required for BBSome assembly, but its depletion enhances BBSome accumulation in cilia. AZI1 knockdown restores BBSome trafficking to cilia in BBS3- or BBS5-depleted cells where the BBSome cannot normally enter cilia. Co-immunoprecipitation, siRNA knockdown, ciliary trafficking assays, zebrafish morpholino knockdown PLoS genetics High 24550735
2015 CEP131 is a direct substrate of the p38 effector kinase MK2; MK2 phosphorylates CEP131 at S47 and S78. UV-induced phosphorylation of these residues creates direct binding sites for 14-3-3 proteins, which sequester CEP131 in the cytoplasm, blocking new centriolar satellite formation and causing rapid depletion of centriolar satellites. Mutation of S47 and S78 abolishes stress-induced centriolar satellite reorganisation. In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation with 14-3-3, immunofluorescence, UV stress experiments Nature communications High 26616734
2019 PLK4 directly phosphorylates CEP131 at Ser-78 in vitro and in cells. PLK4-mediated phosphorylation of Ser-78 is dispensable for CEP131 localization, ciliogenesis, and centriole duplication but is essential for maintaining the integrity of centriolar satellites. PLK4 inhibition or non-phosphorylatable CEP131-S78A causes dispersed satellites; phosphomimetic S78D promotes satellite aggregation. Analog-sensitive PLK4 phosphoproteomic screen, in vitro kinase assay, phospho-site mutagenesis, immunofluorescence microscopy, RPE-1 cell engineering The Journal of biological chemistry High 30804208
2024 Cep131 forms a module with Cep162 near the axoneme at the basal body, and together with the Cby-Fam92 module cooperatively maintains Cep290 at the basal body and initiates ciliogenesis in Drosophila. Concurrent deletion of any protein in the Cep131-Cep162 module and the Cby-Fam92 module causes complete loss of Cep290 from the basal body and blocks ciliogenesis at its initiation stage. Drosophila genetics (double mutants), immunolocalisation, epistasis analysis PLoS biology Medium 38442096
1997 The mouse AZ1 protein (CEP131) is localised to the preacrosome region of spermatids; its gene is transcribed beginning in pachytene spermatocytes. The 5'-proximal region constitutes a CpG island and gene expression is induced by 5-azacytidine (DNA demethylation) in fibroblasts. Immunolocalisation, genomic cloning, RT-PCR, 5-azacytidine treatment Genomics Medium 9070930
2022 CEP131 interacts with the transcription factor ARID3A in liver cancer cells and the ARID3A/CEP131 complex co-occupies the KDM3A promoter to transcriptionally activate KDM3A, which then demethylates H3K9me2 to upregulate embryonic stem cell-like signature genes, promoting cancer cell viability and metastasis. Co-immunoprecipitation, ChIP assay, loss-of-function/gain-of-function in vitro and in vivo Cell death & disease Medium 36008383
2024 CEP131-positive centriolar satellites promote local translation at centrosomes. The RNA binding protein Unkempt localises to Cep131-positive centriolar satellites and is required for Plk4-induced centriole overduplication in an RNA-binding-dependent manner, with Unk and Cep131 together promoting localised translation near centrosomes. Fluorescence microscopy, genetic knockdown, RNA binding domain mutagenesis, translation reporters at centrosomes bioRxivpreprint Low bio_10.1101_2024.07.29.605660
2020 MDM2 interacts with CEP131 and promotes its protein degradation; overexpression of CEP131 accelerates neuroblastoma cell growth and confers resistance to CHK1 inhibitor-induced replication defects. Mass spectrometry (MDM2-binding proteins), overexpression studies, cell growth assays Journal of oncology Low 33014050

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity. Cell reports 148 23602565
2015 Arabidopsis AZI1 family proteins mediate signal mobilization for systemic defence priming. Nature communications 102 26203923
2013 Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct ciliary phenotypes. PLoS genetics 101 24415959
2012 The centriolar satellite protein Cep131 is important for genome stability. Journal of cell science 91 22797915
2013 Salt stress in Arabidopsis: lipid transfer protein AZI1 and its control by mitogen-activated protein kinase MPK3. Molecular plant 86 24214892
2009 Cep70 and Cep131 contribute to ciliogenesis in zebrafish embryos. BMC cell biology 66 19254375
2011 Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation. Journal of cell science 60 21750193
2001 Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock. Critical care medicine 55 11395599
2015 p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1. Nature communications 45 26616734
2014 The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary trafficking of the BBSome. PLoS genetics 35 24550735
2018 Natural allelic variation of the AZI1 gene controls root growth under zinc-limiting condition. PLoS genetics 34 29608565
2008 ODCp, a brain- and testis-specific ornithine decarboxylase paralogue, functions as an antizyme inhibitor, although less efficiently than AzI1. The Biochemical journal 27 18062773
2011 Cold-inducible expression of AZI1 and its function in improvement of freezing tolerance of Arabidopsis thaliana and Saccharomyces cerevisiae. Journal of plant physiology 24 21492954
2019 Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131). The Journal of biological chemistry 22 30804208
2022 Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature. Cell death & disease 20 36008383
2016 Metabolomic analysis reveals the relationship between AZI1 and sugar signaling in systemic acquired resistance of Arabidopsis. Plant physiology and biochemistry : PPB 18 27337039
2016 Post-Translational Modification and Secretion of Azelaic Acid Induced 1 (AZI1), a Hybrid Proline-Rich Protein from Arabidopsis. International journal of molecular sciences 13 26771603
2021 Kinases and protein motifs required for AZI1 plastid localization and trafficking during plant defense induction. The Plant journal : for cell and molecular biology 10 33342031
2024 Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer. Apoptosis : an international journal on programmed cell death 9 39222275
2024 Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation. PLoS biology 7 38442096
2020 CEP131 knockdown inhibits cell proliferation by inhibiting the ERK and AKT signaling pathways in non-small cell lung cancer. Oncology letters 7 32218865
1997 Genomic organization of the mouse AZ1 gene that encodes the protein localized to preacrosomes of spermatids. Genomics 7 9070930
2020 CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma. Journal of oncology 6 33014050
2014 Mitogen-activated protein kinase-regulated AZI1 - an attractive candidate for genetic engineering. Plant signaling & behavior 6 24518841
2012 Molecular characterization, tissue expression and nucleotide variation of the porcine AZ1 gene. Gene 2 22310384