Affinage

AKAP8

A-kinase anchor protein 8 · UniProt O43823

Length
692 aa
Mass
76.1 kDa
Annotated
2026-06-09
39 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKAP8 (AKAP95) is a nuclear matrix scaffold protein that organizes cell-cycle-dependent signaling and chromatin events by anchoring protein kinase A (PKA) and recruiting effector machinery to defined nuclear substrates (PMID:9473338, PMID:10601332). It is nuclear in interphase and redistributes to chromatin at mitosis, where it captures the PKA RIIα subunit through a CDK1-controlled molecular switch: CDK1 phosphorylation of RIIα at T54 governs RIIα anchoring to chromatin-bound AKAP8, and disrupting this anchoring drives premature chromatin decondensation (PMID:9473338, PMID:11591814). At mitosis AKAP8 acts as a chromatin receptor that recruits the condensin complex (via hCAP-D2/Eg7 and XCAP-H) to promote chromosome condensation, using distinct chromatin-binding and condensin-targeting zinc-finger regions (PMID:10601332, PMID:10791967, PMID:11964380). In interphase it interacts with MCM2 to support initiation of DNA replication (PMID:12740381) and associates with MLL1/MLL2 H3K4 methyltransferase complexes—binding the core subunit DPY30—to enhance H3K4 methylation and stimulate transcription (PMID:23995757, PMID:29288530). AKAP8 is also a pre-mRNA splicing regulator that binds proximal intronic RNA through its zinc fingers and scaffolds hnRNP H/F/U proteins to control exon inclusion, inhibiting hnRNPM to enforce an epithelial splicing program whose loss promotes EMT and breast cancer metastasis (PMID:27824034, PMID:31980632). These chromatin and RNA functions depend on AKAP8 forming liquid-like phase-separated condensates: condensate integrity is required for splicing regulation, for recruiting RNA Pol II into transcriptional condensates, and for cancer cell growth, and pharmacological disruption of phase separation attenuates MLL-AF9-driven leukemogenesis (PMID:32719551, PMID:41501053). AKAP8 chromatin association is dynamically released by nuclear tyrosine kinase (Src/Fyn/c-Abl) phosphorylation, linking it to chromatin structural remodeling (PMID:25770215). Beyond anchoring PKA, AKAP8 organizes a nuclear cAMP microdomain together with PDE4D5 (PMID:30982750) and is required for proper spindle assembly checkpoint function via interaction with the nucleoporin TPR (PMID:28379780).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Established that AKAP8 anchors PKA in a cell-cycle-dependent manner, defining it as a nuclear A-kinase anchoring protein rather than a constitutive PKA scaffold.

    Evidence Immunofluorescence and reciprocal Co-IP from synchronized HeLa cells showing mitosis-specific RIIα association

    PMID:9473338

    Open questions at the time
    • Did not define the chromatin substrate or downstream consequence of mitotic PKA anchoring
    • Mechanism of cell-cycle-dependent redistribution unresolved
  2. 1999 High

    Answered what AKAP8 does at mitosis by showing it is required for chromosome condensation and recruits condensin to chromatin, separating a structural role from PKA anchoring.

    Evidence In vitro condensation assays, immunodepletion/rescue from mitotic extract, intranuclear immunoblocking, and Co-IP with Eg7/hCAP-D2

    PMID:10601332

    Open questions at the time
    • Did not map the domains required for chromatin vs condensin binding
    • Relationship between PKA-dependent and PKA-independent condensation roles unclear
  3. 2000 High

    Defined AKAP8 as a concentration-dependent chromatin receptor for condensin, linking the amount of recruited condensin to the extent of condensation.

    Evidence Recombinant C-terminal fragment addition with dose-dependent rescue and GST pull-down of condensin subunits

    PMID:10791967

    Open questions at the time
    • Whether recruitment alone or additional activity drives condensation not resolved
  4. 2001 High

    Resolved the modular architecture and the mitotic switch: a nuclear-matrix-targeting site distinct from DNA/PKA domains, and CDK1 phosphorylation of RIIα T54 controlling anchoring to chromatin.

    Evidence Mutational/nuclear-matrix binding analysis plus RIIα phosphomimetic point mutants with reconstitution and rescue; identification of p68 RNA helicase partner

    PMID:11279182 PMID:11591814

    Open questions at the time
    • How tethering RIIα mechanistically maintains condensation not defined
    • Functional role of p68 helicase interaction not pursued
  5. 2002 Medium

    Dissected the zinc-finger requirements (ZF1 for chromatin binding, ZF2 for condensin targeting) and showed condensin recruitment is necessary but not sufficient for condensation.

    Evidence Systematic deletion/point mutagenesis with in vitro condensation assays and XCAP-H pull-downs; AMY-1 ternary complex suppressing PKA activity

    PMID:11964380 PMID:12414807

    Open questions at the time
    • The additional step beyond recruitment needed for condensation unidentified
    • AMY-1 regulatory mechanism shown in single lab
  6. 2003 High

    Extended AKAP8 function into S phase by showing its N-terminal interaction with MCM2 is required for DNA replication initiation and elongation.

    Evidence Yeast two-hybrid, intranuclear peptide disruption, in vitro replication assay, and dose-dependent recombinant rescue

    PMID:12740381

    Open questions at the time
    • How AKAP8 mechanistically promotes MCM2 chromatin retention not defined
  7. 2004 Medium

    Connected AKAP8 to cell-cycle cyclin regulation by showing direct binding to D- and E-type cyclins displaced by CDKs, defining cyclin–AKAP8–PKA versus cyclin–CDK pools.

    Evidence Yeast two-hybrid, Co-IP across multiple cell types, and CDK competition assays

    PMID:14641107 PMID:16721056

    Open questions at the time
    • Functional consequence of cyclin sequestration on cell-cycle progression untested
    • Single lab
  8. 2006 Medium

    Revealed organismal and inflammatory roles: a genetic interaction with fidgetin required for palatogenesis, and AKAP8-anchored PKA suppressing TLR4-driven TNFα.

    Evidence In vivo mouse genetic epistasis with reciprocal Co-IP; RNAi screening with anchoring inhibitors and p105 phosphorylation analysis

    PMID:16751186 PMID:19531803

    Open questions at the time
    • Molecular basis of the fidgetin-AKAP8 developmental requirement unclear
    • TNFα phosphorylation findings from a single lab
  9. 2013 High

    Established AKAP8 as a positive transcriptional/epigenetic regulator by showing it associates with and directly enhances MLL1/MLL2 H3K4 methyltransferase activity.

    Evidence Biochemical purification, in vitro H3K4 methylation and chromatin transcription assays, Co-IP, and reporter assays in ES cells

    PMID:23995757

    Open questions at the time
    • Direct subunit contact within the MLL complex not yet defined (resolved later as DPY30)
  10. 2015 High

    Identified tyrosine phosphorylation by Src/Fyn/c-Abl as a regulatory switch that dissociates AKAP8 from chromatin and drives chromatin structural changes.

    Evidence Phosphorylation assays, tyrosine-to-phenylalanine mutagenesis, cell fractionation, and RNAi with chromatin structural readouts

    PMID:25770215

    Open questions at the time
    • Which specific tyrosines are physiologically targeted not pinpointed
    • Link to oxidative-stress signaling correlative
  11. 2016 High

    Defined AKAP8 as a direct pre-mRNA splicing regulator and rRNA synthesis modulator, broadening its role beyond chromatin to RNA metabolism.

    Evidence CLIP-seq/RIP showing intronic RNA binding and hnRNP H/F/U interactions; ChIP, SELEX, and FRAP at the nucleolus with rRNA quantification; Cx43 nuclear translocation Co-IP/MS

    PMID:26683827 PMID:26880274 PMID:27824034

    Open questions at the time
    • How RNA binding and chromatin functions are coordinated not resolved
    • rRNA and Cx43 findings from single labs
  12. 2017 Medium

    Refined the nuclear PKA module by defining an AKAP8–PKA–PDE4D5 cAMP microdomain, a TPR-dependent spindle checkpoint role, and a CREB-dependent transcriptional output.

    Evidence FRET cAMP biosensors with PDE pharmacology; BioID/Co-IP and RNAi mitotic-timing phenotypes; siRNA with nuclear PKA/phospho-CREB readouts validated in human amnion tissue

    PMID:28379780 PMID:29162743 PMID:30982750

    Open questions at the time
    • How a single scaffold integrates microdomain, checkpoint, and transcription functions unclear
    • Each finding from a single lab
  13. 2018 Medium

    Pinpointed DPY30 as the physical bridge between AKAP8's PKA-binding domain and H3K4 methyltransferase complexes, mechanizing the earlier MLL association.

    Evidence Co-IP, domain and L69D point mutagenesis, and cell-cycle-synchronized binding assays

    PMID:29288530

    Open questions at the time
    • Whether DPY30 bridging is required for H3K4 methylation enhancement in vivo not directly tested
    • Single lab
  14. 2020 High

    Revealed that AKAP8 function depends on liquid-liquid phase separation and that its splicing program enforces an epithelial cell state suppressing EMT and metastasis.

    Evidence In vitro phase separation, FRAP, condensate-hardening/chimeric rescue, splicing reporters, and growth/senescence assays; hnRNPM inhibition, RNA-seq, and in vivo metastasis assays with CLSTN1 isoform manipulation

    PMID:31980632 PMID:32719551

    Open questions at the time
    • The endogenous sequence determinants of condensation only partially defined
    • Direct mechanistic link between condensate biophysics and specific splicing decisions incomplete
  15. 2023 Medium

    Uncovered a paracrine function in which AKAP8 secreted by FBXW7-mutant cancer cells induces DNA damage in neighboring cells.

    Evidence CRISPR knockout, Transwell co-culture, mass spectrometry identification of secreted AKAP8, and double-knockout abrogation

    PMID:37386001

    Open questions at the time
    • Mechanism of AKAP8 secretion and the receptor/pathway driving DNA damage unknown
    • Single lab
  16. 2024 Medium

    Linked AKAP8 phase separation to a specific transcriptional output controlling PARP1 levels via an hnRNPUL1 short isoform, defining a PARP-inhibitor sensitivity axis.

    Evidence ChIP, RNA-seq, knockdown/rescue, phase separation assays, and PARP inhibitor cytotoxicity assays

    PMID:38711442

    Open questions at the time
    • How AKAP8 condensates select the hnRNPUL1 short isoform mechanistically unclear
    • Single lab
  17. 2026 High

    Established that AKAP8 phase separation and RNA binding recruit RNA Pol II into transcriptional condensates and co-condense with MLL-AF9 to sustain leukemogenesis, validating a therapeutic phase-separation-disrupting peptide.

    Evidence ChIP-seq, RNA-seq, CRISPR knockout, in vitro phase separation, Co-IP, and JD-PI95 peptide leukemogenesis assays

    PMID:41501053

    Open questions at the time
    • Generality of condensate-driven Pol II recruitment beyond MLL-AF9 targets not fully mapped
    • In vivo therapeutic window of JD-PI95 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AKAP8's diverse activities—PKA anchoring, condensin recruitment, replication, H3K4 methylation, splicing, and Pol II condensate formation—are spatiotemporally coordinated by a single phase-separating scaffold remains unresolved.
  • No unified model linking condensate biophysics to substrate selection across cell-cycle phases
  • No structural model of the full-length scaffold with its partners
  • How post-translational switches (CDK1, tyrosine kinases) globally reprogram its functions unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0003723 RNA binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005654 nucleoplasm 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-69306 DNA Replication 1
Partners
CCND3DPY30GJA1HNRNPMMCM2PDE4D5PRKAR2ATPR
Complex memberships
AKAP8-PKA(RIIα)-PDE4D5 complexMLL1/MLL2 H3K4 methyltransferase complexcondensin

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 AKAP95 is localized to the nucleus in interphase cells, while RIIα is excluded from the nucleus; during mitosis, AKAP95 redistributes and co-localizes with RIIα outside the metaphase plate, and RIIα is co-immunoprecipitated with AKAP95 from mitotic but not interphase HeLa cells, demonstrating a cell cycle-dependent physical association. Immunofluorescence microscopy, co-immunoprecipitation from synchronized HeLa cells Experimental cell research High 9473338
1999 AKAP95 associates with the nuclear matrix in interphase and redistributes to chromatin at mitosis; intranuclear immunoblocking of AKAP95 inhibits chromosome condensation in a PKA-independent manner; depletion of AKAP95 from mitotic extract causes premature chromatin decondensation; maintenance of condensed chromatin requires PKA binding to chromatin-associated AKAP95 and cAMP signaling; AKAP95 interacts with Eg7 (hCAP-D2), a component of the condensin complex, and is required for Eg7 recruitment to chromatin. Cell fractionation, in vitro chromosome condensation assay with recombinant AKAP95 fragments, intranuclear immunoblocking, immunodepletion from mitotic extract, co-immunoprecipitation, GST pull-down The Journal of cell biology High 10601332
2000 AKAP95 acts as a targeting/receptor protein for hCAP-D2/Eg7 (condensin component) to chromosomes; recombinant AKAP95 C-terminal fragment binds chromatin and recruits Eg7 in a concentration-dependent manner correlating with extent of chromosome condensation; GST pull-down data suggest AKAP95 recruits multiple condensin subunits. In vitro chromosome condensation assay, recombinant protein addition/rescue, GST pull-down, immunofluorescence co-localization The Journal of cell biology High 10791967
2001 AKAP95 is targeted to the nuclear matrix via a distinct nuclear matrix-targeting site (separate from DNA- and PKA-binding domains); AKAP95 directly binds isolated nuclear matrix in a targeting-site-dependent manner; AKAP95 interacts with p68 RNA helicase both in vitro and in co-immunoprecipitation from cell extracts, with co-localization in the nuclear matrix. Mutational analysis, in situ nuclear matrix binding, yeast two-hybrid, Far Western blot, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 11279182
2001 CDK1 phosphorylates RIIα on threonine 54 (T54) at mitosis, creating a molecular switch that controls RIIα anchoring to chromatin-bound AKAP95; RIIα(T54E) phosphomimetic fails to associate with chromatin-bound AKAP95 at mitosis; disrupting AKAP95-RIIα anchoring promotes premature chromatin decondensation; wild-type RIIα or RIIα(T54D) rescues decondensation in RIIα-deficient cells. Stably transfected RIIα-deficient cell lines with wild-type and point mutants, cell fractionation, in vitro chromatin condensation/decondensation assay, nuclear reconstitution assay Journal of cell science High 11591814
2002 AMY-1 binds to the RII-binding region of AKAP95 in vivo and in vitro, forming a ternary complex with RII; this AMY-1/AKAP95/RII complex prevents the PKA catalytic subunit from binding to the AKAP complex, suppressing PKA activity. Co-immunoprecipitation, in vitro binding assay, PKA activity assay The Journal of biological chemistry Medium 12414807
2002 Chromatin binding of AKAP95 is conferred by residues 387–450 and requires zinc finger ZF1; residues 525–569 are essential for condensation activity and condensin recruitment; ZF2 (C-terminal zinc finger) is required for condensin targeting whereas ZF1 is dispensable for this; AKAP95 interacts with Xenopus XCAP-H condensin subunit in vitro and in vivo but not with human hCAP-D2; condensin recruitment to chromatin is not sufficient to promote condensation. Deletion and point mutant analysis, in vitro chromosome condensation assay, GST pull-down, co-immunoprecipitation EMBO reports High 11964380
2003 AKAP95 interacts with MCM2 (a component of the pre-replication complex) via its N-terminal residues 1–195; disrupting the AKAP95-MCM2 interaction inside HeLa nuclei abolishes initiation of DNA replication in G1 and elongation phase in vitro; depletion of AKAP95 from nuclei partially depletes MCM2 and abolishes replication; recombinant AKAP95 restores intranuclear MCM2 and replication in a dose-dependent manner. Yeast two-hybrid, GST pull-down, co-immunoprecipitation from chromatin, intranuclear peptide disruption, in vitro DNA replication assay, recombinant protein rescue The Journal of biological chemistry High 12740381
2004 AKAP95 physically interacts with all three D-type cyclins (D1, D2, D3) but not with CDK4 or p27kip1; CDK4 displaces the cyclin D3–AKAP95 interaction; endogenous interactions confirmed in thyrocytes, human fibroblasts, and NIH-3T3 cells. Yeast two-hybrid, co-immunoprecipitation from multiple cell types, co-transfection The Biochemical journal Medium 14641107
2006 AKAP95 binds cyclin E1, and G1/S cyclins (D and E) can interact with the RIIα subunit of PKA through AKAP95; CDKs displace cyclins from AKAP95, suggesting distinct cyclin–CDK vs. cyclin–AKAP95–PKA complexes. Co-immunoprecipitation, competition assay with CDKs Cell cycle Medium 16721056
2006 Fidgetin (an AAA ATPase) physically interacts with AKAP95 in the nuclear matrix; genetic interaction between fidgetin and AKAP95 is required for palatogenesis in mice — double mutants (fidget + Akap95 gene-trap) exhibit cleft palate lethality not seen in single mutants. Yeast two-hybrid, co-immunofluorescence, reciprocal co-immunoprecipitation, genetic epistasis in mice (gene trap + existing mutant) The Journal of biological chemistry High 16751186
2009 PKA anchored via AKAP95 suppresses LPS-induced TNF-α production in macrophages; AKAP95-anchored PKA phosphorylates p105 (NF-κB1) at a site adjacent to the IKK target region, thereby suppressing TNFα gene expression downstream of TLR4. Multigene RNAi screening, selective PKA-anchoring inhibitors, time-lapse microscopy, cAMP analog treatment Science signaling Medium 19531803
2013 AKAP95 physically and functionally associates with MLL1 and MLL2 histone methyltransferase complexes; AKAP95 directly enhances MLL2 H3K4 methyltransferase activity in a cell-free chromatin transcription system; ectopic AKAP95 stimulates chromosomal reporter gene expression in synergy with MLL1 or MLL2; AKAP95 depletion impairs retinoic acid-mediated gene induction in embryonic stem cells. Biochemical purification, in vitro H3K4 methylation assay, cell-free chromatin transcription assay, co-immunoprecipitation, siRNA knockdown with reporter assay Nature structural & molecular biology High 23995757
2015 Tyrosine phosphorylation of AKAP8 by nuclear tyrosine kinases (Src, Fyn, c-Abl, nucleus-targeted Lyn/c-Src) dissociates AKAP8 from chromatin and the nuclear matrix; substitution of multiple AKAP8 tyrosines to phenylalanine inhibits its dissociation from nuclear structures and suppresses kinase-induced chromatin structural changes; AKAP8 knockdown increases chromatin structural changes; hydrogen peroxide induces chromatin structural changes accompanied by AKAP8 dissociation. Phosphorylation assays, tyrosine-to-phenylalanine mutagenesis, cell fractionation, chromatin structural change assay, RNAi knockdown The Journal of biological chemistry High 25770215
2016 AKAP95 interacts with hnRNP H/F and U proteins through its N-terminal region, and directly binds preferentially to proximal intronic regions on pre-mRNAs via its zinc-finger domains to promote exon inclusion; AKAP95 also interacts with itself (self-association); AKAP95 is established as a regulator of pre-mRNA splicing and a potential integrator of transcription and splicing. RNA immunoprecipitation (RIP), CLIP-seq/transcriptome-wide analysis, co-immunoprecipitation, RNA splicing assays, RNAi knockdown Nature communications High 27824034
2016 A subpopulation of AKAP95 localizes to the nucleolus during interphase, associates with ribosomal chromatin (ChIP), co-localizes with upstream binding factor (UBF), binds GC-rich DNA in vitro (SELEX), and is a highly mobile protein by FRAP; AKAP95 expression reciprocally regulates 47S rRNA production — AKAP95 is a regulator of ribosomal RNA synthesis. ChIP, SELEX, FRAP, immunofluorescence co-localization, siRNA knockdown with rRNA quantification The FEBS journal Medium 26683827
2016 AKAP95 and Cx43 dynamically interact during cell cycle progression; Cx43 translocates to the nucleus via AKAP95 in late G1; their interaction is reduced by PKA inhibitor H89 and enhanced by forskolin, implicating PKA signaling in the interaction. Co-immunoprecipitation, tandem mass spectrometry, confocal immunofluorescence, Western blot Scientific reports Medium 26880274
2017 AKAP95 forms a nuclear signaling complex with PKA and PDE4D5 that controls a local cAMP microdomain; locally generated cAMP accumulates within this complex, but plasma membrane-generated cAMP is prevented from activating nuclear PKA by PDE4 (local sink) and PDE3 (barrier). FRET-based cAMP biosensor (live cell imaging), pharmacological manipulation of PDE activity, co-immunoprecipitation Cell chemical biology Medium 30982750
2017 AKAP95 interacts with nucleoporin TPR specifically in mitosis (identified by BioID proximity screen and confirmed by Co-IP); AKAP95 depletion causes faster prometaphase-to-anaphase transition, escape from nocodazole-induced mitotic arrest, formation of micronuclei from lagging chromosomes, and partial delocalization of the spindle assembly checkpoint component MAD1 from kinetochores; AKAP95 is required for proper spindle assembly checkpoint function. BioID proximity labeling proteomics, co-immunoprecipitation, RNAi depletion with mitotic timing assays, immunofluorescence for MAD1 kinetochore localization, nocodazole arrest assay Cell cycle Medium 28379780
2017 AKAP95-anchored nuclear PKA is required for cortisol-induced PTGS2 (COX-2) expression in human amnion fibroblasts; cortisol increases AKAP95 expression, expanding the nuclear PKA pool; AKAP95 knockdown reduces nuclear PKA and phospho-CREB, attenuating cortisol-induced PTGS2 expression without affecting STAT3 phosphorylation. siRNA knockdown in primary human amnion fibroblasts, Western blot for nuclear PKA/phospho-CREB/COX-2, qRT-PCR for PTGS2, human tissue analysis (amnion after labor vs. cesarean section) Science signaling Medium 29162743
2018 The PKA-binding domain of AKAP8 is essential for direct interaction with DPY30 (core subunit of H3K4 HMT complexes); a single L69D substitution in DPY30 abolishes its dimerization and interaction with both AKAP8 and BIG1; AKAP8 interacts with DPY30 and RIIα in both interphase and mitotic cells. Co-immunoprecipitation, in vitro binding with domain mutants, point mutagenesis (L69D DPY30), cell cycle-synchronized binding assays The FEBS journal Medium 29288530
2020 AKAP95 forms phase-separated, liquid-like condensates in vitro and in the nucleus; condensate formation is required for its splicing regulatory activity; hardening of condensates significantly impairs splice regulation; substitution of the condensation-mediating region with unrelated condensation-mediating sequences restores activity; AKAP95 condensates are required for supporting cancer cell growth and suppressing oncogene-induced senescence. In vitro phase separation assay, FRAP (fluorescence recovery after photobleaching), condensate-disrupting/hardening mutations, chimeric protein rescue, splicing reporter assays, cell growth and senescence assays Nature cell biology High 32719551
2020 AKAP8 inhibits hnRNPM splicing activity through direct protein-protein interaction, and directly binds RNA to alter splicing outcomes; AKAP8 promotes an epithelial-cell-state splicing program genome-wide; AKAP8 loss promotes EMT-associated alternative splicing and breast cancer metastasis; CLSTN1 is an AKAP8 splicing target whose isoform switch is crucial for EMT. Co-immunoprecipitation (AKAP8-hnRNPM interaction), RNA binding assays, RNA-seq/splicing analysis, shRNA knockdown, metastasis assays in vivo, CLSTN1 isoform manipulation Nature communications High 31980632
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; co-culture with double-mutant FBXW7-/-/AKAP8-/- cells abrogates this paracrine DNA damage. CRISPR-Cas9 knockout, Transwell co-culture, mass spectrometry (identification of secreted AKAP8), AKAP8 overexpression, AKAP8/FBXW7 double knockout Cell death discovery Medium 37386001
2024 AKAP8 is enriched at chromatin and regulates transcription of a specific short isoform of hnRNPUL1 through phase separation; ectopic expression of the hnRNPUL1 short isoform partially rescues growth inhibition caused by AKAP8 knockdown; AKAP8 modulates PARP1 expression through hnRNPUL1, and AKAP8 inhibition enhances PARP inhibitor cytotoxicity. ChIP, RNA-seq, siRNA knockdown, overexpression rescue, PARP inhibitor sensitivity assay, phase separation assay iScience Medium 38711442
2026 AKAP95 phase separation and RNA binding properties modulate RNA Pol II recruitment into transcriptional condensates at genome-wide target sites; AKAP95 interacts with MLL1 translocated fragment (MLL-AF9), and partial co-condensation leads to stronger AKAP95 binding at MLL-AF9 target genes; loss of AKAP95 downregulates MLL-AF9 target gene expression and impairs MLL-AF9-driven leukemogenesis; a peptide (JD-PI95) bridging AKAP95 to HSP70 impairs AKAP95 phase separation and attenuates gene transcription. ChIP-seq, RNA-seq, CRISPR knockout, co-immunoprecipitation, in vitro phase separation, peptide design and functional assay, leukemogenesis assay 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 39 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 24 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 3 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

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