Affinage

ZNF282

Zinc finger protein 282 · UniProt Q9UDV7

Length
671 aa
Mass
74.3 kDa
Annotated
2026-06-11
23 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZNF282 is a Krüppel-type zinc finger transcription factor with context-dependent repressive and activating functions on target gene promoters (PMID:9396811, PMID:25373738). It was first defined as a sequence-specific DNA-binding repressor that recognizes the TCCACCCC core motif of the HTLV-I LTR U5 repressive element and silences LTR-driven transcription through a distinct HUR repressive domain, with the N-terminal region upstream of HUR also required for repression (PMID:9396811). In cancer cells ZNF282 instead promotes proliferation by supporting the E2F1 transcriptional program: it acts as an E2F1 co-activator whose loss impairs E2F1-mediated gene expression, cell cycle progression, migration, invasion, and tumorigenicity (PMID:25373738), and its knockout blocks the G1/S transition while downregulating E2F1 and its targets CCNE1 and CCND1 (PMID:41125417). Beyond DNA binding, transcriptional regulation, and these cell cycle/oncogenic phenotypes, no additional mechanistic detail of ZNF282 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 1997 Medium

    Establishing whether ZNF282 is a sequence-specific DNA-binding factor defined its identity as a transcriptional repressor with a dedicated repression domain.

    Evidence Southwestern blotting, reporter transcription assays, and deletion mapping on the HTLV-I LTR U5RE

    PMID:9396811

    Open questions at the time
    • No structural basis for HUR-domain-mediated repression
    • Corepressor partners recruited by the HUR domain not identified
    • Endogenous (non-viral) target genes bound via the TCCACCCC motif not defined
  2. 2014 Medium

    Linking ZNF282 to E2F1 co-activation reframed it from a repressor to a positive regulator of proliferation in a cancer context.

    Evidence siRNA knockdown with co-activator/reporter assays, cell cycle, migration, and xenograft readouts in esophageal squamous cell carcinoma

    PMID:25373738

    Open questions at the time
    • Whether ZNF282 contacts E2F1 directly or acts through DNA binding not resolved
    • Mechanism reconciling repressive (HUR) and co-activating roles unexplained
  3. 2025 Medium

    CRISPR knockout with rescue placed ZNF282 upstream of E2F1 expression itself, connecting it causally to the G1/S transition and E2F1 target genes.

    Evidence CRISPR/Cas9 knockout and rescue with cell cycle analysis, target profiling (CCNE1, CCND1), and computational motif scanning in colorectal cancer cells

    PMID:41125417

    Open questions at the time
    • Predicted upstream E2F1 binding site is computational only, not confirmed by ChIP
    • Direct occupancy of the E2F1 regulatory region not demonstrated
  4. 2025 Low

    A lncRNA-coupled axis proposed ZNF282 as an activator of proline biosynthesis, extending its transcriptional reach to metabolic targets.

    Evidence RNA pulldown for LINC02878-ZNF282 binding, LINC02878 knockdown, expression/reporter assays, and xenograft model in colorectal cancer

    PMID:41331125

    Open questions at the time
    • Direct transcriptional activation of PYCR2 by ZNF282 not fully reconstituted
    • Single-study axis without independent confirmation
    • Whether LINC02878 binding alters ZNF282 DNA-binding or recruits cofactors unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZNF282 switches between HUR-domain-dependent repression and E2F1/metabolic gene activation, and what cofactors dictate this context dependence, remains unresolved.
  • No molecular explanation for repressor-to-activator switching
  • No genome-wide map of direct ZNF282 binding sites
  • Corepressor/coactivator complexes not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1
Partners
E2F1LINC02878

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ZNF282 (HUB1) binds directly to the U5 repressive element (U5RE) of the HTLV-I LTR, recognizing the TCCACCCC core motif, and strongly represses HTLV-I LTR-mediated transcription. A novel repressive domain (HUR domain) distinct from the KRAB-like domain was identified as required for repression, and the N-terminal region upstream of the HUR domain was also indispensable. Southwestern blotting (protein-DNA binding), reporter gene transcription assays, deletion mapping of repressive domains Nucleic acids research Medium 9396811
2014 ZNF282 functions as a co-activator of E2F1 in esophageal squamous cell carcinoma cells; depletion of ZNF282 inhibited E2F1-mediated gene expression, cell cycle progression, migration, and invasion, and reduced xenograft tumorigenicity. siRNA knockdown, reporter/co-activator assays, xenograft tumor model, cell cycle and migration assays Oncotarget Medium 25373738
2025 ZNF282 binds to the PYCR2 gene locus and activates PYCR2 expression downstream of the lncRNA LINC02878, thereby enhancing proline biosynthesis and promoting colorectal cancer aggressiveness; LINC02878 was shown to bind ZNF282 to mediate this transcriptional activation. RNA pulldown/binding assay (lncRNA-protein interaction), gene knockdown (LINC02878), reporter/expression assays, in vivo xenograft model Cellular and molecular life sciences : CMLS Low 41331125
2025 CRISPR/Cas9 knockout of ZNF282 in colorectal cancer cells impaired the G1/S cell cycle transition and downregulated E2F1 and its downstream targets CCNE1 and CCND1; motif scanning identified a putative ZNF282 binding site upstream of the E2F1 transcription start site, suggesting ZNF282 activates E2F1 expression by facilitating an upstream regulatory region. CRISPR/Cas9 knockout, rescue re-expression, cell cycle analysis, downstream target expression profiling, computational motif scanning Cancer science Medium 41125417

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing. Nature 81 21614000
2004 Ubiquitin-like protein Hub1 is required for pre-mRNA splicing and localization of an essential splicing factor in fission yeast. Current biology : CB 52 15620657
2003 The ubiquitin-like protein HUB1 forms SDS-resistant complexes with cellular proteins in the absence of ATP. EMBO reports 48 14608371
2014 The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells. Journal of molecular cell biology 32 24872507
2004 Hub1 is an essential ubiquitin-like protein without functioning as a typical modifier in fission yeast. Genes to cells : devoted to molecular & cellular mechanisms 32 15569151
2017 Error-Prone Splicing Controlled by the Ubiquitin Relative Hub1. Molecular cell 28 28712727
1997 HUB1, a novel Krüppel type zinc finger protein, represses the human T cell leukemia virus type I long terminal repeat-mediated expression. Nucleic acids research 22 9396811
2010 Complete genome sequence of Mycoplasma hyorhinis strain HUB-1. Journal of bacteriology 21 20802032
2010 The role of the transcript elongation factors FACT and HUB1 in leaf growth and the induction of flowering. Plant signaling & behavior 18 20404555
2020 ESCRT recruitment by the S. cerevisiae inner nuclear membrane protein Heh1 is regulated by Hub1-mediated alternative splicing. Journal of cell science 17 33262311
2019 Stress-induced upregulation of the ubiquitin-relative Hub1 modulates pre-mRNA splicing and facilitates cadmium tolerance in Saccharomyces cerevisiae. Biochimica et biophysica acta. Molecular cell research 16 31666190
2021 UBL5/Hub1: An Atypical Ubiquitin-Like Protein with a Typical Role as a Stress-Responsive Regulator. International journal of molecular sciences 15 34502293
2014 ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma. Oncotarget 15 25373738
1999 HUB1 is an autoantigen frequently eliciting humoral immune response in patients with adult T cell leukemia. International journal of oncology 12 10087317
2022 The ubiquitin-like protein Hub1/UBL-5 functions in pre-mRNA splicing in Caenorhabditis elegans. FEBS letters 7 36480405
2023 Moonlighting functions of the ubiquitin-like protein, Hub1/UBL-5. The international journal of biochemistry & cell biology 5 37453225
2022 Broader roles of the ubiquitin-like protein Hub1 indicated by its yeast two-hybrid interactors. microPublication biology 5 35098049
2012 Is HUB1 a hub for plant fitness? Plant signaling & behavior 3 23073007
2025 Integrative analysis of Hub1 overexpression: driving transcriptional reprogramming and alternative splicing in Saccharomyces cerevisiae. BMC genomics 2 41053551
2025 LINC02878/ZNF282/PYCR2 axis promotes proline synthesis and tumor progression in colorectal cancer. Cellular and molecular life sciences : CMLS 1 41331125
2022 Computer- and NMR-Aided Design of Small-Molecule Inhibitors of the Hub1 Protein. Molecules (Basel, Switzerland) 1 36500376
2025 ZNF282 Promotes Colorectal Cancer Progression Possibly via E2F1 Activation. Cancer science 0 41125417
2024 Correction: Reyes Romero et al. Computer- and NMR-Aided Design of Small-Molecule Inhibitors of the Hub1 Protein. Molecules 2022, 27, 8282. Molecules (Basel, Switzerland) 0 38931013

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