Affinage

ZNF280A

Zinc finger protein 280A · UniProt P59817

Length
542 aa
Mass
60.6 kDa
Annotated
2026-06-11
11 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZNF280A is a chromatin-associated zinc finger protein that operates at the interface of genome maintenance and oncogenic signaling (PMID:40523937, PMID:33414445). Its best-defined molecular function is in DNA double-strand break repair: ZNF280A is recruited to break sites and promotes long-range DNA-end resection during homologous recombination by facilitating recruitment of the BLM-DNA2 helicase-nuclease complex and enhancing its enzymatic activity, such that loss of ZNF280A causes genomic instability and sensitivity to DNA-damaging agents (PMID:40523937). In cancer settings ZNF280A behaves as a tumor-promoting factor that acts through multiple downstream effectors: it sustains EIF3C expression to drive lung adenocarcinoma (PMID:33414445), stabilizes RPS14 against ubiquitin-mediated degradation to engage PI3K-Akt signaling in colorectal cancer (PMID:36059657), and interacts with the transcription factor CUX2 to enhance ACRV1 transcription, activating PI3K/AKT signaling and glycolytic metabolism in ovarian cancer (PMID:41338461). It additionally inactivates Hippo signaling to support proliferation (PMID:30847384). Beyond these contexts, the structural basis of ZNF280A's DNA/chromatin association and its direct transcriptional targets have not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2019 Medium

    Whether ZNF280A had any role in tumor cell proliferation was unknown; this work placed it as a driver of colorectal cancer growth acting through Hippo pathway inactivation.

    Evidence siRNA silencing with luciferase reporter and Western blot for Hippo activity, proliferation assays, and xenografts in colorectal cancer

    PMID:30847384

    Open questions at the time
    • No direct molecular interaction linking ZNF280A to Hippo components
    • Mechanism of pathway regulation (transcriptional vs post-translational) undefined
  2. 2021 Medium

    To identify ZNF280A's pro-tumor effectors, this study established EIF3C as a downstream mediator required for ZNF280A-induced lung adenocarcinoma promotion.

    Evidence Expression profiling after knockdown plus epistasis rescue (EIF3C knockdown in ZNF280A-overexpressing cells) in vitro and in vivo

    PMID:33414445

    Open questions at the time
    • No demonstration that ZNF280A binds the EIF3C locus directly
    • Whether regulation is transcriptional remains unresolved
  3. 2022 Medium

    Building on cancer roles, this work added a post-translational axis whereby ZNF280A protects RPS14 from ubiquitin-mediated degradation to engage PI3K-Akt signaling.

    Evidence Knockdown with ubiquitination assays and Western blot for RPS14 and PI3K-Akt components, functional assays in colorectal cancer cells

    PMID:36059657

    Open questions at the time
    • Mechanism by which ZNF280A controls RPS14 ubiquitination is unknown
    • No identified E3 ligase or direct binding
  4. 2025 High

    The molecular function of ZNF280A had remained obscure; a chromORFeome screen revealed it is a DSB repair factor that promotes long-range resection via the BLM-DNA2 complex.

    Evidence High-throughput microscopy screen, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, and rescue in patient-derived cells

    PMID:40523937

    Open questions at the time
    • No structure of ZNF280A or its DNA/chromatin contacts
    • Direct physical interaction interface with BLM-DNA2 not mapped
    • Relationship between resection role and oncogenic transcriptional roles unresolved
  5. 2025 Medium

    To explain ZNF280A's transcriptional output, this study showed it interacts with CUX2 to enhance ACRV1 transcription and drive PI3K/AKT-linked glycolysis in ovarian cancer.

    Evidence Co-IP between ZNF280A and CUX2, promoter recruitment assay at ACRV1, metabolic assays, and pharmacological AKT/glycolysis rescue

    PMID:41338461

    Open questions at the time
    • Single Co-IP without reciprocal structural validation
    • Whether CUX2 partnership generalizes beyond ovarian cancer unknown
  6. 2025 Low

    This work tested ZNF280A's influence on cell survival in melanoma, linking its loss to p53 upregulation, apoptosis, and cell cycle arrest.

    Evidence shRNA knockdown with Western blot for p53, flow cytometry for apoptosis and cell cycle, and functional assays in melanoma

    PMID:40251414

    Open questions at the time
    • Single method (Western blot) for p53 with limited mechanistic depth
    • No demonstration of direct regulation of p53
    • Not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZNF280A's role in homologous-recombination resection mechanistically connects to its diverse oncogenic transcriptional and post-translational activities remains unresolved.
  • No unifying model linking DSB repair function to tumor-promoting effectors
  • DNA-binding specificity and direct transcriptional targets undefined
  • No structural characterization

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-73894 DNA Repair 1
Partners
BLMCUX2DNA2

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 ZNF280A is recruited to DNA double-strand break (DSB) sites and is essential for DSB repair by homologous recombination. Mechanistically, ZNF280A promotes long-range DNA-end resection by facilitating the recruitment of the BLM-DNA2 helicase-nuclease complex to DSB sites and enhancing the enzymatic activity of this complex at DNA damage sites. Loss of ZNF280A drives genomic instability and sensitivity to DNA-damaging agents. High-throughput microscopy with cDNA 'chromORFeome' library screen, loss-of-function experiments, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, rescue by ZNF280A reintroduction in patient-derived cells Nature cell biology High 40523937
2021 ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C; downregulation of EIF3C in ZNF280A-overexpressed cells attenuated ZNF280A-induced tumor promotion, placing EIF3C as a downstream effector of ZNF280A. Gene expression profiling after ZNF280A knockdown, loss-of-function and overexpression in vitro and in vivo, epistasis rescue experiment (EIF3C knockdown in ZNF280A-overexpressed cells) Cell death & disease Medium 33414445
2019 ZNF280A promotes colorectal cancer cell proliferation by inactivating the Hippo signaling pathway; silencing ZNF280A activated Hippo signaling and suppressed proliferation with G0/G1 arrest. Western blot and luciferase reporter assays for Hippo pathway activity, siRNA-mediated silencing, in vitro proliferation assays, in vivo xenograft Molecular therapy oncolytics Medium 30847384
2022 ZNF280A knockdown promotes the ubiquitination and degradation of RPS14 in colorectal cancer cells, and RPS14 in turn regulates CRC development via the PI3K-Akt signaling pathway, establishing a ZNF280A/RPS14/PI3K-Akt axis. Loss-of-function (ZNF280A knockdown), ubiquitination assays, Western blot for RPS14 protein levels and PI3K-Akt pathway components, in vitro and in vivo functional assays Frontiers in oncology Medium 36059657
2025 ZNF280A enhances ACRV1 transcription by interacting with the transcription factor CUX2 and facilitating CUX2 recruitment to the ACRV1 promoter; elevated ZNF280A or ACRV1 activates PI3K/AKT signaling and increases glycolytic enzyme expression (PKM2, LDHA), glucose uptake, lactate production, and ATP generation in ovarian cancer cells. Co-immunoprecipitation/interaction assays between ZNF280A and CUX2, chromatin recruitment assay to ACRV1 promoter, knockdown/overexpression functional assays, metabolic assays (glucose uptake, lactate, ATP, ECAR), pharmacological AKT/glycolysis inhibition rescue The Journal of biological chemistry Medium 41338461
2025 ZNF280A knockdown in malignant melanoma cells leads to increased apoptosis and cell cycle arrest associated with upregulation of p53 expression, suggesting ZNF280A regulates p53 levels in this context. shRNA-mediated knockdown, Western blot for p53, flow cytometry for apoptosis and cell cycle, in vitro and in vivo functional assays Discover oncology Low 40251414

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling. Blood 137 18984860
2008 Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene. Leukemia research 44 19027161
2021 ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C. Cell death & disease 22 33414445
2019 ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer. Molecular therapy oncolytics 15 30847384
2023 Comprehensive characterization of the embryonic factor LEUTX. iScience 14 36876139
2022 Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14. Frontiers in oncology 9 36059657
2025 ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome. Nature cell biology 4 40523937
2023 Knockdown of ZNF280A inhibits cell proliferation and promotes cell apoptosis of bladder cancer. Histology and histopathology 3 37345848
2025 ZNF280AY: a pseudogene on the ovine Y chromosome and its copy number variation associated with testicular size in Hu sheep. Journal of animal science 1 40514799
2025 ZNF280A promotes malignant melanoma development through regulating cell proliferation, apoptosis, and cell cycle. Discover oncology 0 40251414
2025 ZNF280A and ACRV1 enhance aerobic glycolysis and drive ovarian cancer progression via the PI3K/AKT signaling pathway. The Journal of biological chemistry 0 41338461

Missed literature

Know a paper Affinage missed for ZNF280A? Flag it for the maintainers and the community.

No submissions yet.