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Showing CEP131 — AZI1 is a alias.

CEP131

Centrosomal protein of 131 kDa · UniProt Q9UPN4

Length
1083 aa
Mass
122.1 kDa
Annotated
2026-06-09
16 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

CEP131 (AZI1) is a centriolar satellite protein that supports ciliogenesis, flagellogenesis, and centriole homeostasis across vertebrate and invertebrate systems (PMID:22797915, PMID:24415959). It is recruited to centriolar satellites by PCM1 and positioned at the centriolar core by pericentrin and CEP290, with its centrosomal localization regulated through the cell cycle and dependent on an intact microtubule network and dynein-dynactin transport (PMID:22797915). CEP131 traffics along microtubules to become enriched at the basal body and transition zone, and its loss reduces ciliogenesis and produces intraflagellar-transport-like defects, including shortened cilia and randomized left-right asymmetry, with a flagellum-specific requirement in sperm that drives male infertility in null mice (PMID:24415959, PMID:19254375). At the ciliary base it acts within a Cep131-Cep162 module that, cooperating with a Cby-Fam92 module, maintains CEP290 at the basal body to permit ciliogenesis initiation (PMID:38442096), and it interacts with BBS4 to restrain BBSome ciliary trafficking (PMID:24550735). Centriolar satellite integrity and stress responsiveness are governed by phosphorylation: the p38 effector kinase MK2 phosphorylates CEP131 at Ser-47 and Ser-78 to create 14-3-3 binding sites that sequester it in the cytoplasm and trigger satellite disassembly during UV stress (PMID:26616734), while PLK4 directly phosphorylates Ser-78 to maintain satellite integrity independently of ciliogenesis and centriole duplication (PMID:30804208). Beyond its centrosomal roles, CEP131 functions in a transcriptional context by interacting with ARID3A to co-activate KDM3A in liver cancer cells (PMID:36008383).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 Medium

    Established that Cep131 is required for cilium formation in vivo, placing it functionally alongside intraflagellar transport machinery rather than core centrosome assembly.

    Evidence Morpholino knockdown in zebrafish with ciliary and laterality readouts; yeast two-hybrid screen against HDAC6/IFT proteins

    PMID:19254375

    Open questions at the time
    • No direct molecular partner identified (negative two-hybrid)
    • Mechanism linking Cep131 to IFT not resolved
    • Morpholino specificity not controlled by genetic rescue
  2. 2011 Medium

    Showed the conserved ortholog acts at the ciliary base to regulate intraflagellar transport, generalizing CEP131's ciliary role beyond vertebrates.

    Evidence Drosophila dila mutant analysis, localization, and genetic epistasis with Uncoordinated

    PMID:21750193

    Open questions at the time
    • Biochemical nature of the DILA-Uncoordinated link unknown
    • Direct IFT substrate engagement not demonstrated
  3. 2012 Medium

    Defined how CEP131 is delivered to and retained at centriolar satellites and the centriolar core, and linked its loss to genome instability.

    Evidence siRNA knockdown, co-localization, and functional phenotyping in human cells

    PMID:22797915

    Open questions at the time
    • Mechanism connecting satellite loss to centriole amplification and DNA damage unresolved
    • PCM1/pericentrin/CEP290 recruitment hierarchy correlative
  4. 2013 High

    Distinguished acute from chronic loss and revealed a tissue-specific, flagellum-restricted requirement, demonstrating CEP131 is essential for sperm flagellogenesis but dispensable for cilia in other tissues.

    Evidence siRNA with siRNA-resistant rescue, Azi1 null mouse with EM and live imaging of basal body/transition zone trafficking

    PMID:24415959

    Open questions at the time
    • Molecular basis of tissue-specific dependence unknown
    • Trafficking cargo of CEP131 in the manchette/flagellum not identified
  5. 2014 Medium

    Identified a direct BBS4 interaction through which CEP131 negatively regulates BBSome entry into cilia, providing a molecular handle on its IFT-related function.

    Evidence Co-IP, siRNA epistasis with BBS3/BBS5 depletion, and zebrafish morpholino phenotyping

    PMID:24550735

    Open questions at the time
    • Structural basis of CEP131-BBS4 binding unknown
    • How CEP131 restrains BBSome trafficking mechanistically unresolved
  6. 2015 High

    Demonstrated that CEP131 is the key MK2/14-3-3 target controlling stress-induced centriolar satellite disassembly, defining a regulated mechanism for satellite plasticity.

    Evidence In vitro kinase assay, S47/S78 phosphosite mutagenesis, 14-3-3 co-IP, and UV stress assays

    PMID:26616734

    Open questions at the time
    • Functional consequence of satellite disassembly for downstream signaling not fully defined
    • Whether other satellite proteins are co-regulated unknown
  7. 2019 High

    Resolved a second kinase input by showing PLK4 directly phosphorylates Ser-78 to maintain satellite integrity, separable from ciliogenesis and centriole duplication.

    Evidence Analog-sensitive PLK4 kinase assay, phosphoproteomics, and S78A/S78D mutant analysis

    PMID:30804208

    Open questions at the time
    • How a shared S78 site integrates MK2 versus PLK4 signaling unclear
    • Downstream effectors of satellite aggregation/dispersal unknown
  8. 2022 Medium

    Uncovered a non-centrosomal transcriptional role, with CEP131 partnering ARID3A to activate KDM3A and an embryonic stem-cell gene program in liver cancer.

    Evidence Co-IP, ChIP co-occupancy, reporter assays, and knockdown/xenograft in cancer cells

    PMID:36008383

    Open questions at the time
    • How a satellite protein accesses chromatin not explained
    • Direct DNA binding versus adaptor role for CEP131 undetermined
  9. 2024 Medium

    Extended the basal body model by showing the Cep131-Cep162 module cooperates with the Cby-Fam92 module to retain Cep290 and license ciliogenesis initiation.

    Evidence Drosophila genetic deletion and double-mutant epistasis with immunofluorescence

    PMID:38442096

    Open questions at the time
    • Direct physical interactions within the module not biochemically mapped
    • Conservation of module architecture in vertebrates untested here
  10. 2024 Low

    Proposed that CEP131-positive satellites support localized translation at centrosomes coupled to centriole duplication.

    Evidence Immunofluorescence co-localization with Unkempt and centrosomal translation reporter assays with CEP131 knockdown (preprint)

    PMID:bio_10.1101_2024.07.29.605660

    Open questions at the time
    • Preprint, not peer-reviewed
    • Specific role of CEP131 in translation versus scaffolding not dissected
    • Direct RNA or ribosome association of CEP131 not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEP131's distinct activities—satellite scaffolding, basal body CEP290 retention, BBSome trafficking control, and stress-regulated kinase inputs—are coordinated within a single protein remains unresolved.
  • No structural model of CEP131 or its interaction interfaces
  • Molecular link between satellite integrity and centriole/genome stability unknown
  • Reconciliation of ciliary and transcriptional roles not addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-74160 Gene expression (Transcription) 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
ARID3ABBS4CEP290MDM2MK2PCM1PCNTPLK4
Complex memberships
Cep131-Cep162 basal body modulecentriolar satellites

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 CEP131/AZI1 localizes to centriolar satellites and its centrosomal localization is cell-cycle-regulated, requiring an intact microtubule network and a functional dynein-dynactin transport system. CEP131 is recruited to centriolar satellites by PCM1 and localized to the centriolar core region by both pericentrin and CEP290. Depletion of CEP131 results in reduced proliferation, centriole amplification, increased multipolar mitosis, chromosomal instability, and post-mitotic DNA damage. siRNA knockdown, immunofluorescence, co-localization studies in human cells Journal of cell science Medium 22797915
2013 Acute loss of AZI1/CEP131 by siRNA knockdown in mouse fibroblasts leads to a robust reduction in ciliogenesis, rescued by siRNA-resistant AZI1-GFP. AZI1 localizes to centriolar satellites, traffics along microtubules becoming enriched around the basal body, and also localizes to the transition zone. In AZI1 null mice, sperm flagella development is specifically impaired, causing microtubule-based trafficking defects in the manchette and flagella, resulting in male infertility, while cilia in other tissues are functionally normal. siRNA knockdown, rescue experiment with siRNA-resistant GFP fusion, Azi1 null mouse generation, live imaging, immunofluorescence, electron microscopy PLoS genetics High 24415959
2009 In zebrafish embryos, depletion of Cep131 leads to shortened cilia in multiple tissues (kidney, ear) and randomized left-right asymmetry, phenocopying intraflagellar transport mutants, without eliminating centrosomes or basal bodies. Yeast two-hybrid assays failed to detect interaction with HDAC6 or IFT proteins tested. Morpholino knockdown in zebrafish, yeast two-hybrid (negative result for HDAC6/IFT interaction) BMC cell biology Medium 19254375
2011 Drosophila Dilatory (DILA), a homolog of vertebrate AZI1/CEP131, localizes to the ciliary base including the basal body and transition zone in sensory neurons. Loss of dila causes defects in ciliated sensory neurons and sperm consistent with intraflagellar transport defects. DILA interacts genetically with the ciliary coiled-coil protein Uncoordinated, implicating it in regulating intraflagellar transport at the ciliary base. Drosophila mutant analysis, immunofluorescence localization, genetic epistasis (double mutant with Uncoordinated) Journal of cell science Medium 21750193
2014 AZI1/CEP131 interacts with BBS4 and, through this interaction, with the BBSome complex. AZI1 is not required for BBSome assembly, but its depletion enhances BBSome accumulation in cilia. In BBS3- or BBS5-depleted cells where BBSome cannot enter cilia, AZI1 siRNA knockdown restores BBSome ciliary trafficking. AZI1 knockdown in zebrafish causes BBS-like phenotypes including Kupffer's vesicle abnormalities and melanosome transport delay. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, zebrafish morpholino knockdown PLoS genetics Medium 24550735
2015 CEP131 is a substrate of the p38-effector kinase MK2. Ser-47 and Ser-78 are critical MK2 phosphorylation sites in CEP131. UV-induced phosphorylation of these residues creates direct binding sites for 14-3-3 proteins, which sequester CEP131 in the cytoplasm, blocking formation of new centriolar satellites and leading to rapid depletion of these structures. Mutating S47 and S78 in CEP131 abolishes stress-induced centriolar satellite reorganization, identifying CEP131 as the key regulatory target of MK2 and 14-3-3 in this process. In vitro kinase assay, phosphosite mutagenesis, co-immunoprecipitation, immunofluorescence, cell stress assays Nature communications High 26616734
2019 PLK4 directly phosphorylates CEP131 at Ser-78, as confirmed by in vitro kinase assay using an analog-sensitive PLK4 system. PLK4-mediated phosphorylation of Ser-78 is dispensable for CEP131 localization, ciliogenesis, and centriole duplication, but is essential for maintaining centriolar satellite integrity. PLK4 inhibition or a non-phosphorylatable CEP131-S78A variant causes dispersed centriolar satellites, while a phosphomimetic S78D variant promotes their aggregation. Analog-sensitive kinase system, multiplex phosphoproteomics, in vitro kinase assay, immunofluorescence, phosphomimetic and non-phosphorylatable mutant analysis The Journal of biological chemistry High 30804208
2024 In Drosophila, the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the ciliary membrane cooperatively maintain Cep290 at the basal body and are required for ciliogenesis initiation. Concurrent deletion of any protein from both modules leads to complete loss of Cep290 from the basal body and blocks ciliogenesis initiation. Drosophila genetic deletion, immunofluorescence, double-mutant epistasis analysis PLoS biology Medium 38442096
2022 CEP131 interacts with the transcription factor ARID3A and co-occupies the KDM3A promoter to transcriptionally activate KDM3A, which in turn demethylates H3K9me2 to upregulate embryonic stem cell signature genes in liver cancer cells. Co-immunoprecipitation, ChIP assay, reporter assay, knockdown/overexpression in cancer cell lines and in vivo xenograft Cell death & disease Medium 36008383
2020 MDM2 associates with CEP131 protein and promotes its degradation. Overexpression of CEP131 accelerates neuroblastoma cell growth and confers resistance to CHK1 inhibitor-induced replication defects. Mass spectrometry (MDM2 interactome), co-immunoprecipitation, overexpression in neuroblastoma cell lines Journal of oncology Low 33014050
2024 CEP131-positive centriolar satellites promote local translation at centrosomes. Unkempt (Unk) RNA binding protein localizes to centrosomes and Cep131-positive centriolar satellites, and both Unk and Cep131 promote localized translation at these structures, as part of a translational program required for centriole duplication. Immunofluorescence co-localization, translation reporter assays at centrosomes, knockdown of CEP131 in centriolar satellite translation assays bioRxivpreprint Low bio_10.1101_2024.07.29.605660

Source papers

Stage 0 corpus · 16 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 149 23602565
2013 Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct ciliary phenotypes. PLoS genetics 102 24415959
2012 The centriolar satellite protein Cep131 is important for genome stability. Journal of cell science 92 22797915
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
2015 p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1. Nature communications 46 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
2019 Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131). The Journal of biological chemistry 23 30804208
2022 Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature. Cell death & disease 21 36008383
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 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
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

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