Affinage

AFF4

AF4/FMR2 family member 4 · UniProt Q9UHB7

Length
1163 aa
Mass
127.5 kDa
Annotated
2026-04-28
46 papers in source corpus 24 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AFF4 is the central intrinsically disordered scaffold of the Super Elongation Complex (SEC), orchestrating the release of promoter-proximally paused RNA polymerase II to drive productive transcriptional elongation across diverse developmental and physiological gene programs. AFF4 directly recruits P-TEFb (via CycT1), ELL2, and ENL/AF9 through distinct short hydrophobic binding regions along its disordered axis, assembling a bifunctional elongation complex whose structural architecture has been defined by crystallography and cryo-EM, including the Tat–AFF4–P-TEFb–TAR complex critical for HIV-1 transcription (PMID:20471948, PMID:23251033, PMID:23471103, PMID:27731797, PMID:28134250). AFF4's C-terminal homology domain mediates homodimerization and heterodimerization with AFF1, and its activity is regulated by CDK9 phosphorylation and P70S6K phosphorylation at S831, which enhances ENL/AF9 recruitment to crotonylated histones for gene-specific activation (PMID:31147444, PMID:32128251, PMID:41476161). Gain-of-function missense mutations in AFF4 cause CHOPS syndrome, a developmental disorder sharing molecular pathogenesis with Cornelia de Lange syndrome through disturbed SEC-cohesin-RNAP2 interactions and altered transcriptional elongation (PMID:25730767).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 Medium

    Before AFF4's function was known, its physical association with P-TEFb (CDK9/CycT1) established it as a potential transcriptional elongation factor.

    Evidence Affinity purification of epitope-tagged CDK9 from stably transfected cells followed by mass spectrometry and confirmatory immunoprecipitation

    PMID:12065898

    Open questions at the time
    • Single lab; no functional consequence of the interaction tested
    • Binding surface and stoichiometry undefined
    • Relationship to other P-TEFb-associated factors unclear
  2. 2005 High

    Knockout studies revealed that AFF4 is not merely an accessory factor but an essential transcriptional regulator required for spermatogenesis, demonstrating its physiological importance in vivo.

    Evidence AFF4-deficient mouse model showing arrested spermiogenesis, azoospermia, and loss of protamine/transition protein expression in Sertoli cells

    PMID:16024815

    Open questions at the time
    • Target genes regulated by AFF4 in spermatogenesis not comprehensively defined
    • Whether the elongation function or another activity drives this phenotype was untested
    • Redundancy with AFF1 not addressed
  3. 2010 High

    Biochemical purification of MLL chimera complexes identified AFF4 as the core scaffold of the Super Elongation Complex, resolving how P-TEFb and ELL coexist in a single elongation-activating complex and explaining MLL-rearranged leukemia gene activation.

    Evidence Reciprocal affinity purification/mass spectrometry of multiple MLL chimeras; RNAi knockdown reducing MLL target gene expression; sequential affinity purification demonstrating AFF4 bridges P-TEFb and ELL2

    PMID:20159561 PMID:20471948

    Open questions at the time
    • Precise binding sites on AFF4 for each subunit undefined
    • Whether AFF4 is the only scaffold or shares this role with AFF1 unclear
    • Structural basis of the scaffold function unknown
  4. 2012 High

    Binding-site mapping resolved how AFF4's intrinsically disordered architecture uses distinct short hydrophobic regions to independently recruit CycT1, ELL2, and ENL/AF9, establishing the modular logic of SEC assembly.

    Evidence In vitro binding-site mapping, in vivo Co-IP, and biochemical reconstitution of AFF4 subcomplexes

    PMID:23251033

    Open questions at the time
    • Atomic-resolution structures of each interface not yet available
    • Whether all binding sites are simultaneously occupied in vivo unknown
    • Regulation of assembly/disassembly not addressed
  5. 2013 High

    Crystal structures of the AFF4–P-TEFb and Tat–AFF4–P-TEFb complexes revealed that AFF4 meanders over CycT1 without stable CDK9 contacts, and that Tat and AFF4 cooperatively fold on CycT1 to enhance TAR RNA recognition, explaining the mechanism of HIV transcriptional activation.

    Evidence X-ray crystallography of binary and quaternary complexes with interface mutagenesis, fluorescence anisotropy, and transcription assays

    PMID:23471103 PMID:24727379 PMID:24843025

    Open questions at the time
    • Structure of AFF4 regions beyond the P-TEFb-binding fragment unresolved
    • How Tat-independent SEC activation occurs mechanistically unclear
    • Full-length SEC structure lacking
  6. 2015 High

    The discovery that gain-of-function AFF4 mutations cause CHOPS syndrome—with altered genome-wide SEC, cohesin, and RNAP2 binding—linked AFF4 to a Mendelian developmental disorder and revealed that the SEC physically interacts with the cohesin complex to co-regulate transcriptional elongation.

    Evidence Exome sequencing of CHOPS patients, ChIP-seq for AFF4/cohesin/RNAP2, transcriptome analysis, Co-IP of SEC–cohesin–RNAP2

    PMID:25730767

    Open questions at the time
    • Molecular basis of gain-of-function mutations at the structural level not defined
    • Whether cohesin interaction is direct or mediated through other SEC subunits unclear
    • Tissue-specific consequences not fully explored
  7. 2016 High

    Cryo-EM of the Tat–AFF4–P-TEFb–TAR complex showed that AFF4 helix 2 is allosterically stabilized in the RNA-bound state despite not contacting TAR, explaining the 50-fold enhancement of TAR binding by AFF4 through a conformational relay mechanism.

    Evidence 5.9 Å cryo-EM structure integrated with HDX, RNA SHAPE, SAXS, and binding assays

    PMID:27731797

    Open questions at the time
    • Higher-resolution structure of the full RNA-bound complex needed
    • Whether this allosteric mechanism applies to cellular gene promoters unknown
    • Dynamics of the complex in vivo not captured
  8. 2017 High

    The crystal structure of the AFF4 ELLBow–ELL2 interface revealed how a 50-residue AFF4 segment wraps around ELL2 and identified a cavity at this interface as a potential drug target for disrupting SEC-dependent HIV transcription.

    Evidence 2.0 Å X-ray crystallography with mutagenesis and HIV transcription assays

    PMID:28134250

    Open questions at the time
    • No small molecule targeting this cavity reported
    • Whether ELL1 binds AFF4 identically unknown
    • In vivo consequences of disrupting this specific interface not tested
  9. 2019 High

    Structural characterization of the AFF4 C-terminal homology domain (CHD) revealed a novel TPR-like fold mediating homodimerization and AFF1–AFF4 heterodimerization, with a CDK9-phosphorylated surface loop, establishing that dimerization is functionally required for transactivation.

    Evidence 2.2–2.4 Å crystal structures, dimerization-disrupting mutagenesis abolishing transactivation, in vitro kinase assays

    PMID:31147444 PMID:32128251

    Open questions at the time
    • Functional consequence of CDK9 phosphorylation of the CHD loop in vivo undefined
    • Whether dimeric SEC is the active form on chromatin untested
    • Nucleic acid binding by CHD not validated in vivo
  10. 2023 Medium

    Genome-wide studies established that AFF4 is required globally for Pol II pause release—its depletion decreases Ser2-phosphorylated Pol II across chromatin and increases promoter-proximal pausing—while AFF4 and AFF1 bind distinct genomic positions and antagonistically regulate elongation speed and termination at shared target genes.

    Evidence ChIP-seq, PRO-seq, RNA-seq, CUT&Tag in human cells with AFF4/AFF1 knockdown

    PMID:37528066 PMID:37609817

    Open questions at the time
    • How AFF4 versus AFF1 target selectivity is determined mechanistically unknown
    • Whether the antagonism involves direct competition or indirect regulatory circuits unclear
    • Genome-wide results from single labs not yet independently replicated
  11. 2025 High

    Identification of P70S6K-mediated phosphorylation of AFF4 at S831 revealed a signaling-responsive regulatory switch: phospho-S831 enhances ENL/AF9 YEATS domain recruitment to crotonylated histones, coupling metabolic signaling (insulin/mTOR) to gene-specific transcriptional elongation in osteoblasts.

    Evidence Phosphoproteomics, in vitro kinase assay, Co-IP, ChIP, zebrafish functional screen, osteoblast assays

    PMID:41476161

    Open questions at the time
    • Whether S831 phosphorylation regulates SEC function in non-osteoblast contexts untested
    • Structural basis for how phospho-S831 modulates YEATS domain interaction not defined
    • Crosstalk between S831 and S388 phosphorylation events unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of the intact SEC on chromatin, the mechanism specifying AFF4 versus AFF1 genomic targeting, and the integration of multiple phosphorylation inputs into SEC activity remain unresolved.
  • No full-length SEC structure available
  • Mechanism of gene-specific SEC recruitment beyond individual transcription factors unknown
  • How CDK9, P70S6K, and other kinase inputs are coordinated on AFF4 in vivo is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 1 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
AF9AFF1CCNT1CDK9ELL2ENLFUSMECP2
Complex memberships
Super Elongation Complex (SEC)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 AFF4 is a core component of the Super Elongation Complex (SEC), which includes ELL, P-TEFb, AFF4, and other factors. AFF4 is required for SEC stability and proper transcription by poised RNA polymerase II in metazoans. Knockdown of AFF4 in leukemic cells reduces MLL chimera target gene expression. Biochemical purification of MLL chimeras, mass spectrometry, RNAi knockdown with gene expression readout Molecular cell High 20159561
2010 AFF4 acts as a scaffold bridging P-TEFb and ELL2 in the Tat-P-TEFb complex. Through the bridging functions of Tat and AFF4, P-TEFb and ELL2 combine to form a bifunctional elongation complex that greatly activates HIV-1 transcription. AFF4 can mediate the ELL2-P-TEFb interaction without Tat, albeit inefficiently. Sequential affinity purification, Co-IP, functional transcription assays Molecular cell High 20471948
2002 AFF4 (MCEF) was identified as a binding partner of P-TEFb (CDK9/CyclinT1) by affinity purification from stably transfected cells, and antisera against recombinant MCEF specifically immunoprecipitated P-TEFb. Affinity purification of epitope-tagged CDK9, mass spectrometry, immunoprecipitation Journal of biomedical science Medium 12065898
2012 AFF4 serves as the central scaffold of the HIV-1 Tat elongation complex, recruiting P-TEFb (via CycT1), ELL2, and ENL/AF9 through direct interactions with short hydrophobic regions along its structurally disordered axis. CycT1, ELL2, and ENL/AF9 act as bridging components linking this complex to P-TEFb and the PAF complex. In vitro binding site mapping, Co-IP in vivo, biochemical reconstitution Proceedings of the National Academy of Sciences of the United States of America High 23251033
2013 Crystal structure of a tripartite AFF4-P-TEFb complex revealed that AFF4 meanders over the surface of CycT1 but makes no stable contacts with CDK9. AFF4 is positioned to make direct contacts with HIV Tat, and Tat enhances P-TEFb affinity for AFF4. Interface mutations reduced CycT1 binding and AFF4-dependent transcription. X-ray crystallography, interface mutagenesis, in vitro binding assays, transcription assays eLife High 23471103
2014 Crystal structure of quaternary Tat-P-TEFb-AFF4 complex showed that Tat and AFF4 fold on the surface of CycT1 and interact directly. AFF4 binding in the presence of Tat partially orders the CycT1 Tat-TAR recognition motif and increases Tat-P-TEFb affinity for TAR RNA 30-fold. Interface mutations in AFF1 reduced Tat-AFF1 affinity and Tat-dependent transcription from the HIV promoter. X-ray crystallography, fluorescence anisotropy, mutagenesis, transcription assays eLife High 24843025
2014 Crystal structure of the Tat•AFF4•P-TEFb complex revealed that Tat binding to AFF4•P-TEFb causes concerted structural changes in AFF4 via a shift of CycT1 helix H5' and the AFF4 α-3(10) helix. The Tat-TAR recognition motif (TRM) in CycT1 interacts with both Tat and AFF4, leading to exposure of arginine side chains for TAR RNA binding. X-ray crystallography, structural modeling Cell cycle (Georgetown, Tex.) High 24727379
2016 5.9 Å cryo-EM structure of HIV-1 TAR in complex with Tat, AFF4, CDK9, and CycT1. HDX showed AFF4 helix 2 is stabilized in the TAR complex despite not touching the RNA, explaining how AFF4 enhances TAR binding to the SEC 50-fold. The Tat ARM enters the TAR major groove between the bulge and central loop. cryo-EM structure, hydrogen-deuterium exchange (HDX), RNA SHAPE, SAXS, functional binding assays eLife High 27731797
2017 Crystal structure (2.0 Å) of the ELL2 C-terminal domain bound to its 50-residue binding site on AFF4 (the ELLBow). The ELLBow consists of an N-terminal helix and extended hairpin (elbow joint) that occupies the concave surface of ELL2. The AFF4-ELL2 interface contains a cavity suggestive of a small-molecule binding site. This surface is important for ELL2 to promote HIV-1 Tat-mediated proviral transcription. X-ray crystallography, mutagenesis, functional transcription assays Nature communications High 28134250
2019 Crystal structure of human AFF4 C-terminal homology domain (CHD) at 2.2 Å revealed a novel domain of eight helices distantly related to tetratricopeptide repeat motifs. AFF4-CHD mediates AFF4 homodimerization and AFF1-AFF4 heterodimerization. AFF4-CHD interacts with both RNA and DNA in vitro. A surface loop in AFF4-CHD is a substrate for CDK9 phosphorylation. X-ray crystallography, fluorescence anisotropy, biochemical assays, in vitro kinase assay The Journal of biological chemistry High 31147444
2020 Crystal structure of human AFF4-THD (TPRL with Handle Region Dimerization Domain) at 2.4 Å revealed that α4, α5, α6 helices mediate AFF4 dimerization. Single mutations Phe1014A or Tyr1096A impair AFF4 dimerization and abolish AFF4 transactivation activity, but do not affect interaction with other SEC subunits. X-ray crystallography, mutagenesis, transactivation assays, Co-IP Cell discovery High 32128251
2015 Gain-of-function missense mutations in AFF4 cause CHOPS syndrome with altered genome-wide AFF4, cohesin, and RNAP2 binding patterns similar to Cornelia de Lange syndrome. Direct molecular interaction of the SEC, cohesin, and RNAP2 was demonstrated. CHOPS syndrome and CdLS share a common molecular pathogenesis through disturbed transcriptional elongation. Exome sequencing, ChIP-seq, transcriptome analysis, Co-IP of SEC-cohesin-RNAP2 Nature genetics High 25730767
2007 AFF4 (MCEF) is localized exclusively to the nucleus via three distinct protein sequences encoded by three separate exons. Ectopic expression of AFF4 represses HIV-1 LTR-directed RNA Pol II transcription at the level of Tat-transactivation. EGFP fusion protein live-cell imaging, deletion mutant analysis, HIV-1 LTR transcription assay International journal of biological sciences Medium 17389929
2019 Fused in sarcoma (FUS) interacts with AFF4 in cells and co-localizes with AFF4 within nuclear punctuated condensates. FUS inhibits AFF4/ELL2-mediated HIV transcription activation, and FUS depletion elevates AFF4 and CDK9 occupancy on the viral promoter genome-wide. Co-IP, live-cell imaging, ChIP, HIV transcription assays, CRISPR KO Retrovirology Medium 31238957
2014 A cyclin T1 point mutation (V107E) that cannot bind Hexim1, CDK9, or RNA but retains strong AFF4 binding was identified, demonstrating that AFF4 binds a distinct surface on CycT1 from CDK9. CycT1-V107E enforces HIV transcription repression in T cell lines. Site-directed mutagenesis, binding assays in cells, HIV replication assays Retrovirology Medium 24985467
2005 AFF4 (AF5q31/MCEF) is preferentially expressed in Sertoli cells and is essential for spermatogenesis in mice. AFF4-deficient mice show arrested spermiogenesis, azoospermia, and severely impaired expression of protamine 1, protamine 2, and transition protein 2, indicating AFF4 functions as a transcriptional regulator in testicular somatic cells for male germ cell differentiation. Knockout mouse model, histology, gene expression analysis Molecular and cellular biology High 16024815
2012 AFF4 regulates transcription of the AMPKα2 gene in hypothalamic neurons. Overexpression of AFF4 specifically induces AMPKα2 expression and increases AMPKα2 promoter activity, and AFF4 is required for ghrelin-induced late-phase AMPKα2 expression and downstream ACC phosphorylation. Overexpression and siRNA knockdown in GT1-7 neuronal cells, promoter luciferase assay, western blot The Journal of biological chemistry Medium 22528490
2017 AFF4 binds to the promoter region of ID1 and is required for BMP2-induced BRE luciferase activity, SP7 expression, and ALP activity during osteogenic differentiation of MSCs. AFF1 regulates DKK1 expression by binding to its promoter. AFF1 and AFF4 differentially and antagonistically regulate osteogenic differentiation. ChIP, luciferase reporter assay, siRNA knockdown, overexpression, in vivo bone formation Bone research Medium 28955517
2018 AFF4 promotes tumor-initiation capacity of head and neck squamous cell carcinoma (HNSCC) cells by regulating SOX2. SOX2 expression changes in parallel with AFF4 levels, and SOX2 overexpression rescues inhibited proliferation, migration, invasion, and ALDH activity caused by AFF4 knockdown. siRNA knockdown, overexpression, rescue experiments, cell functional assays Carcinogenesis Medium 29741610
2022 AFF4 directly binds autophagy-related proteins ATG5 and ATG16L1 and promotes their transcription. AFF4 deficiency impedes adipocyte development in adipose-specific knockout mice; depleting ATG5 or ATG16L1 abrogates adipogenesis in AFF4-overexpressing cells, while overexpression of ATG5/ATG16L1 rescues impaired adipogenesis in Aff4-KO cells. Co-IP, ChIP, conditional KO mouse model, rescue experiments, cell differentiation assays PLoS genetics Medium 36149892
2023 CDK9-mediated phosphorylation of AFF4 at S388 promotes recruitment of AFF4 by PAX2 to drive expression of HPRT1 and IMPDH2 (nucleotide metabolism enzymes) in pancreatic cancer cells. PI3K/c-Myc axis is required for AFF4 expression. Phosphorylation assays, ChIP, rescue experiments, xenograft model, RNA profiling International journal of biological sciences Medium 37063434
2024 AFF4 and AFF1 have distinct genomic binding patterns (AFF1 upstream of TSS, AFF4 downstream). AFF4 disruption causes slow elongation and early termination in a subset of AFF4-bound active genes, while AFF1 deletion leads to fast elongation and readthrough on the same gene subset. AFF1 knockdown increases AFF4 chromatin levels and vice versa, showing antagonistic regulation. ChIP-seq, PRO-seq, RNA-seq, CUT&Tag, siRNA knockdown Journal of molecular cell biology Medium 37528066
2023 AFF4 knockdown in HEL cells globally decreases CTD serine 2-phosphorylated Pol II chromatin occupancy and increases promoter-proximal Pol II pausing on both heat-shock and non-heat-shock genes. AFF4 promotes pause release by facilitating P-TEFb binding to Pol II. ChIP-seq, PRO-seq, RNA-seq, CUT&Tag, RNAi knockdown Yi chuan = Hereditas Medium 37609817
2025 P70S6K phosphorylates AFF4 at S831 in an insulin-dependent manner in osteoblasts. Phosphorylation of S831 is attenuated in aged, insulin-resistant bone, and is defective in IR osteoblasts. Phospho-S831 AFF4 increases recruitment of chromatin remodelers ENL/AF9 to crotonylated histones via the YEATS domain, promoting gene-specific transcriptional elongation activation. Phosphoproteomics, in vitro kinase assay, Co-IP, ChIP, zebrafish functional screen, osteoblast cell assays Nature communications High 41476161
2024 MeCP2 physically interacts with AFF4 (the SEC scaffold) directly via its transcriptional repression domain. Loss of MeCP2 in mouse cortex reduces AFF4 binding specifically on a subset of synaptic genes, which also show the strongest decrease in Pol II genebody binding. Co-IP in human cells and mouse brain, ChIP-seq, Drosophila genetic modifier screen bioRxivpreprint Medium
2024 SF3B1 inhibition reduces chromatin association of AFF4 (an interaction partner of P-TEFb), contributing to decreased P-TEFb recruitment to chromatin through multiple pathways. Pharmacological inhibition, ChIP, nuclear fractionation bioRxivpreprint Low

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Molecular cell 477 20159561
2010 HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Molecular cell 336 20471948
2019 The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network. Oncogene 323 30659266
2015 Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nature genetics 114 25730767
1999 AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23). Proceedings of the National Academy of Sciences of the United States of America 103 10588740
2012 HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proceedings of the National Academy of Sciences of the United States of America 78 23251033
2013 The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat. eLife 75 23471103
2014 AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter. eLife 50 24843025
2014 Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4. Cell cycle (Georgetown, Tex.) 49 24727379
2020 The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells. Stem cells international 47 32676121
2019 CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis. Aging 46 31848327
2016 Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex. eLife 45 27731797
2002 MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein. Journal of biomedical science 43 12065898
2021 Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis. Cell death & disease 41 34145212
2017 AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs. Bone research 39 28955517
2018 AFF4 promotes tumorigenesis and tumor-initiation capacity of head and neck squamous cell carcinoma cells by regulating SOX2. Carcinogenesis 32 29741610
2017 Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription. Nature communications 32 28134250
2019 Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization. The Journal of biological chemistry 30 31147444
2005 Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia. Molecular and cellular biology 26 16024815
2019 Long noncoding RNA ZFPM2-AS1 is involved in lung adenocarcinoma via miR-511-3p/AFF4 pathway. Journal of cellular biochemistry 23 31692047
2002 A novel infant acute lymphoblastic leukemia cell line with MLL-AF5q31 fusion transcript. Leukemia 20 12399976
2021 MiR-425-5p accelerated the proliferation, migration, and invasion of ovarian cancer cells via targeting AFF4. Journal of ovarian research 19 34686190
2020 AFF4 regulates osteogenic differentiation of human dental follicle cells. International journal of oral science 18 32606293
2003 Insertion of MLL sequences into chromosome band 5q31 results in an MLL-AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemia. Genes, chromosomes & cancer 18 12759932
2019 Fused in sarcoma silences HIV gene transcription and maintains viral latency through suppressing AFF4 gene activation. Retrovirology 16 31238957
2012 Regulation of AMP-activated protein kinase signaling by AFF4 protein, member of AF4 (ALL1-fused gene from chromosome 4) family of transcription factors, in hypothalamic neurons. The Journal of biological chemistry 14 22528490
2023 PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism. International journal of biological sciences 12 37063434
2007 MCEF is localized to the nucleus by protein sequences encoded within three distinct exons, where it represses HIV-1 Tat-transactivation of LTR-directed transcription. International journal of biological sciences 11 17389929
2022 AFF4 regulates cellular adipogenic differentiation via targeting autophagy. PLoS genetics 10 36149892
2022 CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway. Molecular medicine (Cambridge, Mass.) 10 36401176
2020 Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription. Cell discovery 10 32128251
2021 AFF4 facilitates melanoma cell progression by regulating c-Jun activity. Experimental cell research 9 33417923
2014 A single point mutation in cyclin T1 eliminates binding to Hexim1, Cdk9 and RNA but not to AFF4 and enforces repression of HIV transcription. Retrovirology 9 24985467
2023 AFF4 regulates osteogenic potential of human periodontal ligament stem cells via mTOR-ULK1-autophagy axis. Cell proliferation 8 37731335
2024 Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation. Journal of molecular cell biology 6 37528066
2024 N6-methyladenosine-modified circCDK14 promotes ossification of the ligamentum flavum via epigenetic modulation by targeting AFF4. Cellular and molecular life sciences : CMLS 6 39414635
2020 AFF4 enhances odontogenic differentiation of human dental pulp cells. Biochemical and biophysical research communications 6 32139123
2021 Identification of the transcription factor, AFF4, as a new target of miR-203 in CNS. International journal of biological macromolecules 4 33878354
2025 AFF4 promotes tumor progression and cisplatin resistance by modulating the PTEN/PI3K/AKT/mTOR axis to accelerate glycolysis in lung adenocarcinoma. Cell & bioscience 3 40790766
2024 The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression. Combinatorial chemistry & high throughput screening 2 37815186
2023 Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review. International journal of molecular sciences 2 38203475
2025 Phosphoproteomics of aged insulin-resistant bone identifies P70S6K phosphorylation of AFF4 as a gene-specific transcriptional regulator. Nature communications 1 41476161
2024 FENDRR represses Bladder Cancer Cell Proliferation, Stemness, Migration, Invasion, and EMT Process by Targeting miR-18a-5p/AFF4 Axis. Biochemical genetics 1 39572480
2025 Cinobufagin regulates the microRNA-149-3p/AFF4 axis to affect the proliferation and apoptosis of cisplatin-resistant ovarian cancer cells. Journal of chemotherapy (Florence, Italy) 0 40432319
2025 Identification of a novel de novo AFF4 variant (c.778A>G) associated with CHOPS syndrome. Intractable & rare diseases research 0 40904637
2023 AFF4 globally affects the release of paused RNA polymerase II in HEL cells. Yi chuan = Hereditas 0 37609817