Affinage

AKAP8

A-kinase anchor protein 8 · UniProt O43823

Length
692 aa
Mass
76.1 kDa
Annotated
2026-04-28
39 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKAP8 (AKAP95) is a nuclear scaffold protein that organizes signaling, chromatin, and RNA-processing compartments through its capacity to bind chromatin, anchor kinase complexes, recruit chromatin-modifying machinery, and form functionally essential liquid-like phase-separated condensates. It tethers PKA (via RIIα) and PDE4D5 into a nuclear cAMP microdomain that controls local PKA signaling, thereby regulating processes including NF-κB1 phosphorylation downstream of TLR4, CREB-dependent PTGS2 induction, and chromatin condensation maintenance during mitosis (PMID:9473338, PMID:30982750, PMID:19531803, PMID:29162743). Independently of PKA, AKAP8 recruits condensin to chromatin through its zinc-finger and C-terminal domains to drive mitotic chromosome condensation, scaffolds MCM2 for DNA replication initiation, associates with MLL1/MLL2 complexes (via DPY30) to stimulate H3K4 methylation and transcriptional activation, and regulates pre-mRNA splicing by binding proximal intronic RNA and scaffolding hnRNP proteins—including antagonizing the EMT-promoting splicing factor hnRNPM to enforce an epithelial splicing program (PMID:10601332, PMID:12740381, PMID:23995757, PMID:27824034, PMID:31980632). The liquidity and dynamicity of AKAP8 phase-separated condensates are required for its splice-regulatory and transcriptional functions—including modulation of RNA Pol II recruitment and MLL-AF9-driven leukemogenesis—and are regulated by tyrosine phosphorylation (Src, Fyn, Abl) that dissociates AKAP8 from chromatin (PMID:32719551, PMID:41501053, PMID:25770215).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing that AKAP8 is a cell-cycle-regulated nuclear PKA anchor resolved how PKA RIIα reaches chromatin specifically during mitosis.

    Evidence Recombinant binding assays, competitive peptide displacement, and co-IP from synchronized HeLa cells showed cell-cycle-dependent RIIα–AKAP95 interaction at metaphase.

    PMID:9473338

    Open questions at the time
    • Identity of the kinase(s) responsible for cell-cycle switching of the interaction was not defined here
    • Nuclear versus cytoplasmic AKAP95 pools were not quantified
  2. 1999 High

    Demonstrating that AKAP95 is required for chromosome condensation—independently of its PKA-anchoring role—and recruits condensin to chromatin established AKAP95 as a direct mitotic chromatin organizer.

    Evidence Immunoblocking, immunodepletion/rescue with recombinant C-terminal fragment, and co-IP showed AKAP95-dependent condensin (Eg7/hCAP-D2) recruitment in cell-free mitotic extracts.

    PMID:10601332 PMID:10791967

    Open questions at the time
    • Structural basis of AKAP95-condensin interaction unknown
    • Whether AKAP95 is needed for condensation in intact cells in vivo not tested
  3. 2001 High

    Mapping the nuclear matrix targeting domain and identifying p68 RNA helicase as a partner revealed that AKAP95 uses separable domains for DNA binding, PKA binding, and matrix attachment, broadening its scaffold concept.

    Evidence Mutational analysis, yeast two-hybrid, Far Western, and co-IP identified distinct AKAP95 domains and the p68 interaction.

    PMID:11279182

    Open questions at the time
    • Functional consequence of p68 interaction for RNA processing was not tested
    • No structural data on domain boundaries
  4. 2001 High

    Identifying CDK1-mediated T54 phosphorylation of RIIα as a switch for its anchoring to chromatin-bound AKAP95 explained how the mitotic kinase cascade licenses PKA signaling at chromosomes.

    Evidence Phospho-mutant RIIα series in RII-deficient cells with chromatin fractionation, co-IP, and chromatin decondensation rescue.

    PMID:11591814

    Open questions at the time
    • Whether additional phosphorylation events on AKAP95 itself regulate this interaction was not tested
  5. 2002 High

    Dissecting zinc-finger requirements showed that distinct AKAP95 ZF motifs mediate chromatin binding versus condensin recruitment, resolving how a single scaffold can serve both functions.

    Evidence Systematic ZF deletion/mutation in cell-free condensation assays with GST pull-down for condensin subunit binding.

    PMID:11964380

    Open questions at the time
    • Atomic-resolution structure of ZF-chromatin interface not available
    • Condensin subunit specificity (XCAP-H vs. hCAP-D2) remains ambiguous across studies
  6. 2003 High

    Discovering the AKAP95–MCM2 interaction and its necessity for DNA replication initiation extended AKAP95's function from mitosis to S-phase, establishing it as a replication scaffold.

    Evidence Yeast two-hybrid, GST pull-down, depletion/rescue in nuclear replication assays, and intranuclear peptide injection.

    PMID:12740381

    Open questions at the time
    • Whether AKAP95-MCM2 interaction is regulated by PKA phosphorylation was not determined
    • In vivo replication fork dynamics not examined
  7. 2009 High

    An RNAi screen linking AKAP95-anchored PKA to NF-κB1/p105 phosphorylation and TNF-α suppression defined a specific nuclear PKA signaling output relevant to innate immunity.

    Evidence Multigene RNAi screen, cAMP analogs, PKA-anchoring disruptors, and substrate phosphorylation mapping in macrophages.

    PMID:19531803

    Open questions at the time
    • Whether other AKAPs contribute redundantly in macrophages was not fully resolved
    • Direct phosphorylation of p105 by AKAP95-anchored PKA not reconstituted in vitro
  8. 2013 High

    Showing that AKAP95 associates with MLL1/MLL2 complexes and directly stimulates H3K4 methyltransferase activity revealed a chromatin-modifying function beyond structural scaffolding.

    Evidence Purified complex reconstitution with in vitro HMT assay, cell-free transcription assay, co-IP, and RNAi in ES cells.

    PMID:23995757

    Open questions at the time
    • Mechanism by which AKAP95 stimulates enzymatic activity (allosteric vs. substrate presentation) not resolved
    • Genome-wide target genes not defined at this stage
  9. 2015 High

    Demonstrating that tyrosine phosphorylation by Src/Fyn/Abl dissociates AKAP95 from chromatin and the nuclear matrix established a regulatory input that modulates its scaffold functions and chromatin structure.

    Evidence Nucleus-targeted kinase expression, Tyr→Phe mutagenesis, chromatin/matrix fractionation, and siRNA with chromatin structural readouts.

    PMID:25770215

    Open questions at the time
    • Specific tyrosine residue(s) that are functionally critical not definitively identified
    • Downstream consequences for splicing or replication not tested
  10. 2016 High

    Genome-wide CLIP-seq and splicing analysis revealed that AKAP95 binds proximal intronic RNA through its zinc fingers and scaffolds hnRNP H/F/U proteins to promote exon inclusion, establishing a major role in co-transcriptional RNA processing.

    Evidence CLIP-seq, RNA splicing assays, co-IP of hnRNP partners, domain deletion analysis, genome-wide splicing profiling.

    PMID:27824034

    Open questions at the time
    • Structural basis of RNA recognition unknown
    • Relationship between DNA-binding and RNA-binding activities of the same ZF domains unclear
  11. 2017 High

    FRET-biosensor studies showed that AKAP95 co-organizes PKA and PDE4D5 into a nuclear microdomain that controls local cAMP, explaining how nuclear and cytoplasmic cAMP pools are insulated.

    Evidence Targeted FRET-based cAMP biosensors, pharmacological PDE inhibition, and co-IP in intact cells.

    PMID:30982750

    Open questions at the time
    • Whether PDE4D5 binding to AKAP95 is direct or through PKA not fully resolved
    • Microdomain composition beyond PKA/PDE4D5 not characterized
  12. 2020 High

    Showing that AKAP8 antagonizes hnRNPM to enforce an epithelial splicing program—and that its loss drives EMT and breast cancer metastasis—provided a direct link between AKAP8 splice regulation and cancer progression.

    Evidence Co-IP (AKAP8–hnRNPM), RNA-IP, genome-wide splicing analysis, RNAi/overexpression with EMT and in vivo metastasis assays, CLSTN1 isoform manipulation.

    PMID:31980632

    Open questions at the time
    • Whether AKAP8–hnRNPM antagonism is through competitive RNA binding or direct inhibition not fully dissected
    • Patient-level correlation between AKAP8 loss and metastasis not established
  13. 2020 High

    Reconstituting AKAP95 phase separation and showing that condensate liquidity—not mere condensation—is essential for splicing and tumorigenesis support established biophysical properties of condensates as a functional requirement.

    Evidence In vitro phase separation with FRAP/FCS, condensation-disrupting and hardening mutations, heterologous domain swaps restoring function, splicing and tumor growth assays.

    PMID:32719551

    Open questions at the time
    • Molecular determinants distinguishing liquid from hardened condensates not mapped at residue level
    • How condensate properties influence hnRNP recruitment mechanistically is unknown
  14. 2024 Medium

    Linking AKAP8 phase separation to transcriptional control of a specific hnRNPUL1 isoform and downstream PARP1 expression defined a condensate-mediated transcriptional pathway with therapeutic relevance for PARP-inhibitor sensitization.

    Evidence ChIP, RNA-seq isoform analysis, phase separation assays, siRNA/overexpression, PARP inhibitor sensitivity assays in ovarian cancer cells.

    PMID:38711442

    Open questions at the time
    • Mechanism by which condensates select hnRNPUL1 isoform not clarified
    • Single-lab finding not independently validated
    • In vivo drug combination efficacy not tested
  15. 2026 High

    Demonstrating that AKAP95 condensates recruit RNA Pol II and co-condense with MLL-AF9 to activate leukemogenic transcription—and that a designed peptide disrupting these condensates attenuates leukemogenesis—unified the phase-separation, chromatin, and transcriptional functions into a targetable mechanism.

    Evidence ChIP-seq, RNA-seq, FRAP/phase separation assays, co-IP, CRISPR/RNAi in leukemia models, designed peptide (JD-PI95) condensate perturbation.

    PMID:41501053

    Open questions at the time
    • Selectivity of JD-PI95 for AKAP95 condensates versus other nuclear condensates not established
    • Whether AKAP95 condensate function in normal hematopoiesis limits therapeutic window unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of AKAP8 condensates and zinc fingers, the mechanism by which condensate biophysical properties dictate partner recruitment, and whether AKAP8's splicing, transcriptional, and mitotic functions are coordinated or separable in vivo.
  • No atomic-resolution structure of AKAP8 or its condensates
  • Relative in vivo contributions of splicing versus transcriptional functions to tumorigenesis not dissected
  • Integration of tyrosine-phosphorylation regulation with phase-separation behavior not studied

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 4 GO:0005654 nucleoplasm 3 GO:0005730 nucleolus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-69306 DNA Replication 1
Partners
DDX5DPY30HNRNPH1HNRNPMMCM2NCAPD2PDE4DPRKAR2A
Complex memberships
Condensin complex (via XCAP-H/hCAP-D2)MLL1/MLL2 histone methyltransferase complexPKA-RIIα/PDE4D5 nuclear signaling complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 AKAP95 (AKAP8) binds the RIIα regulatory subunit of PKA via a C-terminal domain (amino acids 414-692), and this interaction is cell cycle-dependent: RIIα co-immunoprecipitates with AKAP95 from mitotic but not interphase HeLa cells, with AKAP95 redistributing from nucleus to co-localize with RIIα during metaphase. Recombinant protein binding assay, competitive peptide displacement (Ht31), immunofluorescence, co-immunoprecipitation from synchronized HeLa cells Experimental cell research High 9473338
1999 AKAP95 plays a PKA-independent role in mitotic chromosome condensation: intranuclear immunoblocking of AKAP95 inhibits chromosome condensation and causes premature chromatin decondensation; condensation is rescued by a recombinant C-terminal AKAP95 fragment (residues 387-692). AKAP95 also recruits the condensin component Eg7 (hCAP-D2) to chromatin, and maintenance of condensed chromatin additionally requires PKA binding to chromatin-associated AKAP95 and cAMP signaling. Intranuclear immunoblocking, immunodepletion from mitotic extract, recombinant fragment rescue, co-immunoprecipitation, chromatin fractionation The Journal of cell biology High 10601332
2000 AKAP95 acts as a receptor/targeting protein for the condensin component hCAP-D2/Eg7 to chromatin in mitosis; recombinant AKAP95 (C-terminal 306 aa) directly binds chromatin and recruits Eg7 in a concentration-dependent manner that correlates with chromosome condensation. GST pull-down suggests AKAP95 also recruits additional condensin subunits. Immunofluorescence co-localization, GST pull-down, recombinant protein addition to mitotic extract, immunodepletion/rescue The Journal of cell biology High 10791967
2001 AKAP95 is targeted to the nuclear matrix via a domain distinct from its DNA-binding and PKA-binding domains. AKAP95 directly binds isolated nuclear matrix in a nuclear-matrix-targeting-site-dependent manner and associates with p68 RNA helicase in the nuclear matrix, as shown by yeast two-hybrid, in vitro association, and co-immunoprecipitation from cell extracts. Mutational analysis, in situ nuclear matrix binding assay, yeast two-hybrid, Far Western, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 11279182
2001 CDK1-mediated threonine-54 (T54) phosphorylation of RIIα acts as a molecular switch controlling RIIα anchoring to chromatin-bound AKAP95 at mitosis. T54-phosphorylated RIIα co-fractionates with chromatin-bound AKAP95; T54 mutants fail to associate with AKAP95 at mitosis and fail to rescue premature chromatin decondensation in RIIα-deficient cells. Stable transfection of wild-type and phospho-mutant RIIα in RIIα-deficient Reh cells, chromatin fractionation, co-immunoprecipitation, nuclear reconstitution assay, mitotic extract Journal of cell science High 11591814
2002 Zinc finger ZF1 of AKAP95 is required for chromatin binding (residues 387-450) and chromosome condensation, while ZF2 is required for condensin targeting. Residues 525-569 are essential for condensation activity and condensin recruitment. AKAP95 interacts with Xenopus XCAP-H condensin subunit in vitro and in vivo, but not with hCAP-D2. Deletion and zinc-finger mutation analysis, chromatin-binding assay, chromosome condensation assay in cell-free extract, co-immunoprecipitation, GST pull-down EMBO reports High 11964380
2002 AMY-1 (c-Myc-binding protein) competes with the RII regulatory subunit for binding to the RII-binding region of AKAP95 in the nucleus, forming a ternary AMY-1/AKAP95/RII complex that prevents the catalytic subunit from binding, thereby suppressing PKA activity. Co-immunoprecipitation in vivo and in vitro, competitive binding assays, concentration-dependent binding analysis The Journal of biological chemistry Medium 12414807
2003 AKAP95 interacts with the pre-replication complex component MCM2 (mapped to AKAP95 residues 1-195), and this interaction is required for initiation of DNA replication in G1 and the elongation phase in vitro. Disrupting the AKAP95-MCM2 interaction or depleting AKAP95 abolishes replication and depletes intranuclear MCM2; replication is restored dose-dependently by recombinant AKAP95. Yeast two-hybrid, GST precipitation, co-immunoprecipitation from chromatin, intranuclear peptide injection, AKAP95 depletion/rescue in nuclear replication assay The Journal of biological chemistry High 12740381
2004 AKAP95 interacts with D-type cyclins (D1, D2, D3) but not CDK4 or p27kip1, and CDK4 displaces the cyclin D3-AKAP95 interaction. Interaction with endogenous cyclins D1 and D3 was confirmed in thyrocytes, fibroblasts, and NIH-3T3 cells. Yeast two-hybrid, co-immunoprecipitation in multiple cell lines, co-transfection/co-IP in CHO cells The Biochemical journal Medium 14641107
2006 AKAP95 binds cyclin E1 in addition to D-type cyclins, and these G1/S cyclins interact with the RIIα subunit of PKAα through AKAP95. CDKs displace the cyclin-AKAP95 interaction, suggesting mutually exclusive complexes (cyclin-CDK vs. cyclin-AKAP95-PKA-RIIα). Co-immunoprecipitation, competitive displacement assays Cell cycle Medium 16721056
2006 AKAP95 physically interacts with fidgetin (an AAA-ATPase) in the nuclear matrix, as shown by yeast two-hybrid and reciprocal immunoprecipitation with co-localization; double Akap95/fidget mutant mice exhibit cleft palate, indicating in vivo functional cooperation. Yeast two-hybrid, reciprocal co-immunoprecipitation, immunofluorescence co-localization, genetic epistasis (double mutant mouse) The Journal of biological chemistry High 16751186
2009 AKAP95 (acting as PKA-AKAP95 scaffold) mediates PKA-dependent phosphorylation of p105 (NF-κB1/Nfkb1) at a site adjacent to the IKK-targeted region, suppressing TNF-α gene expression downstream of TLR4 activation in macrophages. cAMP analogs, PKA anchoring inhibitors, and RNAi screening identified this specific AKAP95-PKA pathway. Multigene RNAi screen, cAMP analog pharmacology, selective PKA anchoring inhibitors, time-lapse microscopy, phosphorylation mapping Science signaling High 19531803
2013 AKAP95 physically and functionally associates with MLL1 and MLL2 histone methyltransferase complexes, directly enhancing their H3K4 methyltransferase activity in a cell-free system. Ectopic AKAP95 stimulates chromosomal reporter gene expression synergistically with MLL1/MLL2, and AKAP95 depletion impairs retinoic acid-induced gene expression in embryonic stem cells. Protein complex purification, in vitro H3K4 methyltransferase assay, cell-free chromatin transcription assay, co-immunoprecipitation, RNAi knockdown, reporter gene assay Nature structural & molecular biology High 23995757
2015 Tyrosine phosphorylation of AKAP8 (by Src, Fyn, c-Abl but not Syk) promotes its dissociation from chromatin and the nuclear matrix. Nucleus-targeted tyrosine kinases dissociate AKAP8 from nuclear structures in a kinase-activity-dependent manner; phenylalanine substitution of AKAP8 tyrosines inhibits dissociation and suppresses nuclear tyrosine kinase-induced chromatin structural changes. AKAP8 knockdown increases chromatin structural changes. Nucleus-targeted kinase expression, site-directed mutagenesis (Tyr→Phe), chromatin/nuclear matrix fractionation, immunofluorescence, siRNA knockdown, H2O2 stimulation The Journal of biological chemistry High 25770215
2016 AKAP95 regulates pre-mRNA splicing by binding preferentially to proximal intronic regions of pre-mRNAs (requiring its zinc-finger domains) and scaffolding hnRNP H/F and U proteins through its N-terminal region to promote exon inclusion genome-wide. AKAP95 also directly interacts with itself. RNA immunoprecipitation/CLIP-seq, RNA splicing assays, co-immunoprecipitation of hnRNP partners, domain deletion/mutation analysis, genome-wide splicing analysis Nature communications High 27824034
2016 A subpopulation of AKAP95 localizes to the nucleolus during interphase and associates with the rRNA transcription factor upstream binding factor (UBF). AKAP95 binds GC-rich DNA and ribosomal chromatin in vivo (ChIP), and its expression level reciprocally regulates 47S rRNA production. AKAP95 exhibits RNA Pol I and II-dependent nucleolar trafficking (FRAP). Immunofluorescence co-localization, SELEX, in vitro DNA binding, ChIP, FRAP, AKAP95 over-expression and knockdown with rRNA quantification The FEBS journal Medium 26683827
2017 AKAP95 forms a nuclear microdomain complex with PKA and PDE4D5 that controls local cAMP concentrations. Locally generated cAMP accumulates near this complex, but plasma-membrane-derived cAMP is prevented from activating nuclear PKA by PDE4 (local sink) and PDE3 (barrier). FRET-based cAMP biosensors, targeted cAMP production, pharmacological inhibition of PDE4/PDE3, co-immunoprecipitation Cell chemical biology High 30982750
2017 AKAP95 anchors nuclear PKA in amnion fibroblasts and is essential for cortisol-induced PTGS2 (COX-2) expression via PKA-mediated phosphorylation of CREB. Cortisol increases AKAP95 expression to elevate nuclear PKA abundance; AKAP95 knockdown reduces nuclear PKA, pCREB, and PTGS2 induction but not cortisol-induced pSTAT3. siRNA knockdown, Western blot, nuclear fractionation, chromatin immunoprecipitation, human amnion tissue analysis post-labor Science signaling High 29162743
2017 AKAP95 interacts with the nuclear pore complex protein TPR during mitosis (identified by BioID proximity proteomics), and AKAP95 depletion causes partial delocalization of the SAC component MAD1 from kinetochores, faster prometaphase-to-anaphase transition, escape from nocodazole-induced arrest, and micronuclei from lagging chromosomes, establishing AKAP95 as a regulator of the spindle assembly checkpoint. BioID proximity proteomics, co-immunoprecipitation, siRNA depletion, mitotic timing assays, immunofluorescence of SAC components, nocodazole arrest Cell cycle Medium 28379780
2018 The PKA-binding domain of AKAP8 is essential for direct interaction with DPY30, the core subunit of H3K4 histone methyltransferase complexes. A single L69D substitution in DPY30 disrupts its dimerization and abolishes binding to AKAP8. AKAP8 interacts with DPY30 and RIIα in both interphase and mitotic cells. AKAP8L (a homologue) also interacts with H3K4 HMT complex core subunits. Co-immunoprecipitation, site-directed mutagenesis (DPY30 L69D), interaction mapping with domain deletions, cell-cycle-staged interaction analysis The FEBS journal Medium 29288530
2020 AKAP8 inhibits the splicing activity of the EMT-promoting splicing regulator hnRNPM through direct protein-protein interaction, and also directly binds RNA to alter splicing outcomes. AKAP8 promotes an epithelial-cell-state splicing program genome-wide; its loss promotes EMT and breast cancer metastasis. Manipulation of an AKAP8 splicing target, CLSTN1, confirmed that isoform switching is functionally important for EMT. Co-immunoprecipitation (AKAP8-hnRNPM), RNA immunoprecipitation, genome-wide splicing analysis (RNA-seq), RNAi/overexpression with EMT and metastasis assays, CLSTN1 isoform manipulation Nature communications High 31980632
2020 AKAP95 forms phase-separated, liquid-like condensates in vitro and in nucleus that are required for its splice-regulatory activity and for supporting tumorigenesis and suppressing oncogene-induced senescence. Mutations that disrupt or harden condensates abolish or impair splicing activity, respectively; splicing activity and tumorigenesis support is regained by substituting the condensation-mediating region with heterologous condensation domains, establishing that appropriate biophysical properties (liquidity/dynamicity) of condensates are essential for function. In vitro phase separation assays (FRAP, fluorescence correlation spectroscopy), condensation-disrupting/hardening mutations, domain-swap rescue experiments, splicing assays, tumor growth assays, oncogene-induced senescence assays Nature cell biology High 32719551
2023 AKAP8 is secreted by FBXW7 mutant colorectal cancer cells and induces DNA damage in neighboring wildtype cells. Overexpression of AKAP8 in wildtype cells recapitulates the DNA damage phenotype, and FBXW7-/-/AKAP8-/- double knockout cells lose the ability to induce DNA damage in co-cultured wildtype cells. CRISPR-Cas9 knockout, Transwell co-culture, mass spectrometry identification of secreted proteins, AKAP8 overexpression, AKAP8 knockout rescue experiment Cell death discovery Medium 37386001
2024 AKAP8 is enriched at chromatin and regulates the transcription of a specific short isoform of hnRNPUL1 through phase separation-mediated condensation. The hnRNPUL1 short isoform in turn modulates PARP1 expression, and AKAP8 inhibition enhances PARP inhibitor sensitivity in ovarian cancer cells. ChIP, RNA-seq isoform analysis, phase separation assays, siRNA knockdown, overexpression rescue, PARP inhibitor sensitivity assays iScience Medium 38711442
2026 AKAP95 phase separation and RNA-binding properties modulate RNA Pol II recruitment into transcriptional condensates at target genomic loci. AKAP95 interacts with the MLL1 translocation fragment (MLL-AF9), and partial co-condensation leads to stronger AKAP95 association with MLL-AF9 target genes. Loss of AKAP95 downregulates MLL-AF9 targets and impairs MLL-AF9-driven leukemogenesis. A designed peptide (JD-PI95) bridging AKAP95 to HSP70 impairs AKAP95 phase separation and attenuates gene transcription. ChIP-seq, RNA-seq, FRAP/phase separation assays, co-immunoprecipitation, CRISPR/RNAi loss-of-function in leukemia models, designed peptide condensate perturbation Nature communications High 41501053

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Science signaling 161 19531803
2020 Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis. Nature cell biology 139 32719551
1999 The A-kinase-anchoring protein AKAP95 is a multivalent protein with a key role in chromatin condensation at mitosis. The Journal of cell biology 110 10601332
1998 Molecular cloning, chromosomal localization, and cell cycle-dependent subcellular distribution of the A-kinase anchoring protein, AKAP95. Experimental cell research 97 9473338
2020 The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing. Nature communications 92 31980632
2000 A kinase-anchoring protein (AKAP)95 recruits human chromosome-associated protein (hCAP)-D2/Eg7 for chromosome condensation in mitotic extract. The Journal of cell biology 63 10791967
2001 A-kinase-anchoring protein AKAP95 is targeted to the nuclear matrix and associates with p68 RNA helicase. The Journal of biological chemistry 58 11279182
2013 Regulation of transcription by the MLL2 complex and MLL complex-associated AKAP95. Nature structural & molecular biology 51 23995757
2002 Distinct but overlapping domains of AKAP95 are implicated in chromosome condensation and condensin targeting. EMBO reports 44 11964380
2003 Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator of DNA replication. The Journal of biological chemistry 43 12740381
2019 AKAP95 Organizes a Nuclear Microdomain to Control Local cAMP for Regulating Nuclear PKA. Cell chemical biology 37 30982750
2002 AMY-1 interacts with S-AKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex. The Journal of biological chemistry 35 12414807
2006 G1/S Cyclins interact with regulatory subunit of PKA via A-kinase anchoring protein, AKAP95. Cell cycle (Georgetown, Tex.) 32 16721056
2006 Interaction between fidgetin and protein kinase A-anchoring protein AKAP95 is critical for palatogenesis in the mouse. The Journal of biological chemistry 32 16751186
2001 Regulation of anchoring of the RIIalpha regulatory subunit of PKA to AKAP95 by threonine phosphorylation of RIIalpha: implications for chromosome dynamics at mitosis. Journal of cell science 32 11591814
2016 Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells. Scientific reports 29 26880274
2016 AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors. Nature communications 28 27824034
2004 A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95. The Biochemical journal 27 14641107
2015 Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in Its Dissociation from Chromatin and the Nuclear Matrix. The Journal of biological chemistry 23 25770215
2015 Expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in esophageal cancer and their association with the clinical and pathological parameters. International journal of clinical and experimental medicine 23 26221272
2017 AKAP95-mediated nuclear anchoring of PKA mediates cortisol-induced PTGS2 expression in human amnion fibroblasts. Science signaling 18 29162743
2015 Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase. International journal of clinical and experimental pathology 18 26823747
2015 Synergistic effects of AKAP95, Cyclin D1, Cyclin E1, and Cx43 in the development of rectal cancer. International journal of clinical and experimental pathology 17 25973052
2015 Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L. PloS one 16 26076356
2018 miR-21 enhances the protective effect of loperamide on rat cardiomyocytes against hypoxia/reoxygenation, reactive oxygen species production and apoptosis via regulating Akap8 and Bard1 expression. Experimental and therapeutic medicine 14 30680008
2020 Cx43 and AKAP95 regulate G1/S conversion by competitively binding to cyclin E1/E2 in lung cancer cells. Thoracic cancer 11 32338437
2018 PKA-binding domain of AKAP8 is essential for direct interaction with DPY30 protein. The FEBS journal 11 29288530
2000 cDNA cloning of a novel human gene NAKAP95, neighbor of A-kinase anchoring protein 95 (AKAP95) on chromosome 19p13.11-p13.12 region. Journal of human genetics 11 10697960
2016 AKAP95 promotes cell cycle progression via interactions with cyclin E and low molecular weight cyclin E. American journal of translational research 10 27158371
2013 [Relationship between AKAP95, cyclin E1, cyclin D1, and clinicopathological parameters in lung cancer tissue]. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 8 24370359
2017 AKAP95 interacts with nucleoporin TPR in mitosis and is important for the spindle assembly checkpoint. Cell cycle (Georgetown, Tex.) 7 28379780
2016 A-kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA synthesis. The FEBS journal 7 26683827
2023 Biallelic FBXW7 knockout induces AKAP8-mediated DNA damage in neighbouring wildtype cells. Cell death discovery 5 37386001
2022 Arsenic induces bronchial epithelial carcinogenesis with mitochondrial dysfunction through AKAP95-mediated cell cycle alterations. Toxicology and applied pharmacology 5 35842138
2012 DNA methylation, histone modifications and behaviour of AKAP95 during mouse oocyte growth and upon nuclear transfer of foreign chromatin into fully grown prophase oocytes. Folia biologica 4 23342911
2024 AKAP8 promotes ovarian cancer progression and antagonizes PARP inhibitor sensitivity through regulating hnRNPUL1 transcription. iScience 3 38711442
2024 AKAP95 regulates ubiquitination and degradation of cyclin Ds/Es, influencing the G1/S transition of lung cancer cells. Molecular carcinogenesis 2 38923703
2025 AKAP95: A multifunctional scaffold kinase anchoring protein, role in pathophysiology and perspectives for its therapeutic use. Pharmacological research 1 40846143
2026 AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis. Nature communications 0 41501053