Affinage

GTF3C6

General transcription factor 3C polypeptide 6 · UniProt Q969F1

Round 2 corrected
Length
213 aa
Mass
24.0 kDa
Annotated
2026-04-28
28 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF3C6 (TFIIIC35) is the sixth and final subunit of human transcription factor IIIC (TFIIIC), the multi-subunit complex required for promoter recognition and RNA polymerase III-dependent transcription. Affinity-purified TFIIIC containing epitope-tagged GTF3C6 is active in binding and transcribing the VA1 gene in vitro, and GTF3C6 interacts directly with the TFIIIC63 subunit and more weakly with TFIIIC90 (PMID:17409385). In lung adenocarcinoma, GTF3C6 expression is upregulated downstream of oncogenic KRAS via PI3K signaling, and GTF3C6 promotes anchorage-independent growth, migration, and invasion through activation of FAK phosphorylation; its knockdown suppresses tumor growth in vivo (PMID:38685529).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2007 High

    Identification of GTF3C6 as the sixth TFIIIC subunit resolved the complete subunit composition of human TFIIIC and established that the complex requires this conserved component for promoter binding and RNA Pol III transcription.

    Evidence Molecular cloning, affinity purification of TFIIIC from epitope-tagged TFIIIC35-expressing cells, in vitro transcription of the VA1 gene, and direct in vitro binding assays with individual TFIIIC subunits

    PMID:17409385

    Open questions at the time
    • Structural basis of the GTF3C6–TFIIIC63 interaction is unresolved
    • Contribution of GTF3C6 to TFIIIC assembly or stability in vivo has not been dissected
    • Whether GTF3C6 contacts DNA or other Pol III machinery components is unknown
  2. 2024 Medium

    Linking GTF3C6 to KRAS-driven oncogenesis established a non-canonical, cancer-relevant function: KRAS activates GTF3C6 expression via PI3K, and GTF3C6 in turn promotes malignant phenotypes through FAK pathway activation.

    Evidence Knockdown and overexpression in LUAD cell lines, LSL-KrasG12D/+;LSL-p53−/− mouse model, patient-derived organoids, in vivo tumor growth assays, Western blot for FAK phosphorylation

    PMID:38685529

    Open questions at the time
    • Whether FAK activation by GTF3C6 is direct or mediated through Pol III-dependent transcription of specific targets is unknown
    • Independent replication in additional KRAS-mutant cancer models has not been reported
    • Mechanism by which PI3K signaling upregulates GTF3C6 expression is not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural role of GTF3C6 within the TFIIIC complex and the mechanistic link between its canonical Pol III transcription function and its oncogenic activity remain open questions.
  • No high-resolution structural data for GTF3C6 within TFIIIC exist
  • Whether the cancer phenotype depends on GTF3C6's role in Pol III transcription or an independent function is untested
  • Genome-wide identification of GTF3C6-dependent Pol III transcripts has not been performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140223 general transcription initiation factor activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 1
Partners
GTF3C2GTF3C4
Complex memberships
TFIIIC

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 GTF3C6 (TFIIIC35) was identified and cloned as the sixth subunit of human TFIIIC, the last of the six TFIIIC subunits conserved from yeast. Affinity-purified TFIIIC from an epitope-tagged TFIIIC35 cell line was active in binding to and transcribing the VA1 gene in vitro, confirming its incorporation into a functional complex. TFIIIC35 was shown to interact directly and specifically with TFIIIC subunit TFIIIC63, and to a lesser extent with TFIIIC90, in vitro. Molecular cloning, affinity purification, in vitro transcription assay, in vitro binding/interaction assays, phylogenetic analysis The Journal of biological chemistry High 17409385
2024 GTF3C6 expression is driven by KRAS mutation via the PI3K signaling pathway in lung adenocarcinoma (LUAD). GTF3C6 promotes anchorage-independent proliferation, migration, and invasion of LUAD cells, and its downstream effector is the FAK (focal adhesion kinase) pathway, as GTF3C6 regulates FAK phosphorylation. GTF3C6 knockdown reverses the malignant phenotype of KRAS-mutant LUAD cells in vitro and suppresses tumor growth in vivo. Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, gene knockdown/overexpression, LSL-KrasG12D/+;LSL-p53-/- mouse model, patient-derived organoids, in vivo tumor growth assays Journal of advanced research Medium 38685529

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
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
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
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
2012 A census of human soluble protein complexes. Cell 689 22939629
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
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2016 Dynamic Protein Interactions of the Polycomb Repressive Complex 2 during Differentiation of Pluripotent Cells. Molecular & cellular proteomics : MCP 64 27634302
2016 CHK2-BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly. Proceedings of the National Academy of Sciences of the United States of America 49 26831064
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2007 Identification, molecular cloning, and characterization of the sixth subunit of human transcription factor TFIIIC. The Journal of biological chemistry 35 17409385
2005 Proteomic analysis of SRm160-containing complexes reveals a conserved association with cohesin. The Journal of biological chemistry 29 16159877
2016 TNIP2 is a Hub Protein in the NF-κB Network with Both Protein and RNA Mediated Interactions. Molecular & cellular proteomics : MCP 28 27609421
2020 SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity. Journal of immunology (Baltimore, Md. : 1950) 27 32393512
2021 mTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in Energy Metabolism Caused by FH Loss in RPE Cells. Antioxidants (Basel, Switzerland) 22 34943047
2022 Cullin 3 Exon 9 Deletion in Familial Hyperkalemic Hypertension Impairs Cullin3-Ring-E3 Ligase (CRL3) Dynamic Regulation and Cycling. International journal of molecular sciences 18 35563538
2021 Interactome profiling reveals interaction of SARS-CoV-2 NSP13 with host factor STAT1 to suppress interferon signaling. Journal of molecular cell biology 18 34687317
2006 Vaccines for lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 17 17409835
2016 Quantitative Proteomics of the SMAD (Suppressor of Mothers against Decapentaplegic) Transcription Factor Family Identifies Importin 5 as a Bone Morphogenic Protein Receptor SMAD-specific Importin. The Journal of biological chemistry 15 27703004
2014 LINKIN, a new transmembrane protein necessary for cell adhesion. eLife 13 25437307
2023 USP9X deubiquitinates and stabilizes CDC123 to promote breast carcinogenesis through regulating cell cycle. Molecular carcinogenesis 8 37314216
2016 Identification and function analysis of the host cell protein that interacted with Orf virus Bcl-2-like protein ORFV125. Research in veterinary science 5 27663376
2024 KRAS/PI3K axis driven GTF3C6 expression and promotes LUAD via FAK pathway. Journal of advanced research 2 38685529