Affinage

TAF1D

TATA box-binding protein-associated factor RNA polymerase I subunit D · UniProt Q9H5J8

Round 2 corrected
Length
278 aa
Mass
32.1 kDa
Annotated
2026-04-28
30 papers in source corpus 3 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF1D is an integral subunit of the SL1 complex (also called TIF-IB), the RNA polymerase I-specific transcription factor that nucleates preinitiation complex assembly at the rDNA promoter. Co-purification, reciprocal co-immunoprecipitation, and immunodepletion/reconstitution experiments demonstrate that TAF1D is required for SL1 stability at the rDNA promoter, Pol I recruitment, and pre-rRNA synthesis (PMID:17318177). TAF1D also interacts with DNA polymerase β in the nucleus, and its knockdown produces anti-proliferative and cell-cycle effects in tumor cells (PMID:15520167). In MYCN-amplified neuroblastoma, TAF1D acts as a transcriptional activator of G2/M cell-cycle genes including CDK1, and its depletion causes G2/M arrest and suppresses tumor growth in xenograft models (PMID:37094904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2004 Medium

    Before TAF1D's role in rDNA transcription was known, its initial characterization revealed it as a nuclear protein that physically interacts with DNA polymerase β — establishing that it participates in nuclear protein networks and that its depletion affects cell growth.

    Evidence Yeast two-hybrid screen with co-immunoprecipitation confirmation, GFP-fusion localization, and siRNA knockdown with cell-cycle analysis in human tumor cell lines

    PMID:15520167

    Open questions at the time
    • Functional consequence of the pol β interaction is unknown — no enzymatic or repair assay was performed
    • Expression claimed to be tumor-specific but tested in limited tissue panel
    • No reciprocal knockdown of pol β to test whether the interaction is biologically required
  2. 2007 High

    The central mechanistic question — what TAF1D does at the molecular level — was resolved by showing it is a bona fide SL1 subunit essential for Pol I preinitiation complex formation and rRNA transcription, filling a gap in the composition of the human SL1 complex.

    Evidence Co-purification and reciprocal co-immunoprecipitation with SL1 subunits; immunodepletion from nuclear extracts abolished Pol I transcription (rescued by recombinant SL1); siRNA knockdown displaced SL1 and Pol I from the rDNA promoter by ChIP and reduced pre-rRNA synthesis

    PMID:17318177

    Open questions at the time
    • Structural basis of TAF1D's integration into SL1 is unresolved — no crystal or cryo-EM structure
    • Whether TAF1D contacts the rDNA promoter directly or only through other SL1 subunits is unknown
    • Relationship between the pol β interaction and SL1 function was not explored
  3. 2023 Medium

    Beyond its canonical role in Pol I transcription, TAF1D was found to function as a context-dependent transcriptional activator of Pol II-transcribed G2/M genes in MYCN-amplified neuroblastoma, revealing a previously unrecognized role in cell-cycle gene regulation and tumor proliferation.

    Evidence siRNA knockdown combined with RNA-seq showing downregulation of G2/M genes including CDK1; xenograft mouse model demonstrating tumor growth suppression; colony formation and cell-cycle arrest assays in MYCN-amplified versus non-amplified neuroblastoma lines

    PMID:37094904

    Open questions at the time
    • No direct ChIP or promoter-binding assay for TAF1D at CDK1 or other G2/M gene promoters — activation could be indirect
    • Whether this Pol II-gene regulatory function operates through SL1 or through an independent mechanism is unknown
    • Single-lab finding; not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of TAF1D within the SL1 complex, whether its pol β interaction is functionally relevant, and by what mechanism it activates Pol II-transcribed cell-cycle genes in neuroblastoma.
  • No structural model of TAF1D within SL1
  • Pol β interaction function remains uncharacterized
  • Mechanism linking a Pol I factor to Pol II gene activation is entirely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140223 general transcription initiation factor activity 1
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 2
Partners
CDK1POLBTBP
Complex memberships
SL1 (TIF-IB)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 TAF1D (then called TAF(I)41 / MGC5306) was identified as a novel subunit of the RNA polymerase I transcription factor SL1. It co-purifies and co-immunoprecipitates with SL1, resides at the rDNA promoter in the nucleolus, and is required for Pol I transcription: immunodepletion of TAF(I)41 from nuclear extracts drastically reduces Pol I transcription (rescued by adding recombinant SL1), and siRNA-mediated knockdown in cells causes loss of SL1 from the rDNA promoter, displacement of Pol I from the rDNA, and reduced pre-rRNA synthesis. Co-purification, reciprocal co-immunoprecipitation, immunodepletion/reconstitution in vitro transcription assay, siRNA knockdown with ChIP and pre-rRNA synthesis readout The EMBO Journal High 17318177
2004 TAF1D (MGC5306) was identified as a nuclear protein that interacts with DNA polymerase beta (polβ), including both wild-type polβ and a truncated cancer-associated form (polβΔ), as demonstrated by yeast two-hybrid screening and confirmed by co-immunoprecipitation/Western blot. TAF1D localizes to the nucleus (shown by GFP fusion), is expressed in human carcinomas and tumor cell lines but not normal tissues, and siRNA-mediated knockdown produces anti-growth effects and modulation of cell-cycle events. Yeast two-hybrid screen, co-immunoprecipitation/Western blot, GFP-fusion nuclear localization, siRNA knockdown with cell-cycle analysis Cancer Research Medium 15520167
2023 In MYCN-amplified neuroblastoma cells, TAF1D functions as a transcriptional activator of G2/M phase genes, including the master cell-cycle regulator CDK1. siRNA knockdown of TAF1D more robustly inhibited proliferation and colony formation in MYCN-amplified versus non-amplified NB cells, suppressed tumor growth in a xenograft mouse model, and RNA-seq revealed downregulation of G2/M transition genes and consequent cell-cycle arrest at G2/M. Targeted siRNA screening, RNA-seq, xenograft mouse model, cell-cycle analysis, colony formation assay Cancer Science Medium 37094904

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2007 A novel TBP-associated factor of SL1 functions in RNA polymerase I transcription. The EMBO journal 79 17318177
2016 High-throughput analyses of hnRNP H1 dissects its multi-functional aspect. RNA biology 50 26760575
2020 RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation. Proceedings of the National Academy of Sciences of the United States of America 47 32513696
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2017 The E3 ubiquitin ligase APC/CCdh1 degrades MCPH1 after MCPH1-βTrCP2-Cdc25A-mediated mitotic entry to ensure neurogenesis. The EMBO journal 24 29150431
2011 Quantitative proteomics identifies the Myb-binding protein p160 as a novel target of the von Hippel-Lindau tumor suppressor. PloS one 23 21386990
2022 HDLBP Promotes Hepatocellular Carcinoma Proliferation and Sorafenib Resistance by Suppressing Trim71-dependent RAF1 Degradation. Cellular and molecular gastroenterology and hepatology 19 36244648
2022 The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis. Scientific reports 18 35915203
2004 A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype. Cancer research 10 15520167
2026 Developmental convergence and divergence in human stem cell models of autism. Nature 7 41611887
2025 RNF112 Facilitates Ubiquitin-Mediated Degradation of c-Myc, Suppressing Proliferation, Migration and Lipid Synthesis in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40178292
2023 TAF1D promotes proliferation by transcriptionally activating G2/M phase-related genes in MYCN-amplified neuroblastoma. Cancer science 4 37094904
2022 A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation. International journal of molecular sciences 3 36232890
2025 Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids. Nature communications 2 40593736