Affinage

ANAPC4

Anaphase-promoting complex subunit 4 · UniProt Q9UJX5

Length
808 aa
Mass
92.1 kDa
Annotated
2026-06-09
15 papers in source corpus 2 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANAPC4 acts as a tumor suppressor in papillary thyroid cancer, where its expression restrains cell proliferation, migration, and invasion, and its overexpression inhibits tumor growth in vivo (PMID:38425244). It functions downstream of the tRNA methyltransferase TRMT13, whose levels positively control ANAPC4 abundance and whose anti-tumorigenic effect is mediated through ANAPC4 (PMID:38425244). Beyond this regulatory placement and its tumor-suppressive cellular phenotype, the biochemical and structural basis of ANAPC4's activity has not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2021 Low

    An exome-sequencing screen of HER2-positive breast cancer cells asked which mutations track with therapy resistance, implicating an ANAPC4 variant in trastuzumab sensitivity.

    Evidence Exome and single-cell targeted sequencing with functional sensitivity assays in BT-474 cells

    PMID:33905021

    Open questions at the time
    • ANAPC4 E16K effect is not separated from the concurrent MFSD11 L242I mutation
    • no mechanism linking the variant to resistance established
    • single lab, single method without isogenic validation
  2. 2024 Medium

    Loss- and gain-of-function experiments established ANAPC4 as a tumor suppressor in papillary thyroid cancer, defining a concrete cellular role.

    Evidence siRNA knockdown, overexpression, proliferation/migration/invasion assays, and nude mouse xenograft

    PMID:38425244

    Open questions at the time
    • no biochemical or structural mechanism for the tumor-suppressive activity
    • relationship to APC/C catalytic function not addressed
    • single lab, single cancer type
  3. 2024 Medium

    Epistasis experiments placed ANAPC4 downstream of TRMT13, showing TRMT13 controls ANAPC4 levels and signals through it.

    Evidence TRMT13 knockdown/overexpression with ANAPC4 rescue in papillary thyroid cancer cells and xenografts

    PMID:38425244

    Open questions at the time
    • molecular mechanism by which TRMT13 regulates ANAPC4 expression unknown
    • no direct biochemical interaction demonstrated
    • whether regulation is via tRNA methylation-dependent translation not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The catalytic or scaffolding role of ANAPC4 within the APC/C and how it executes tumor suppression remain undefined.
  • no structural model of ANAPC4 within APC/C
  • no substrates or direct partners identified
  • mechanism connecting TRMT13 regulation to cell-cycle control unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 TRMT13 (a tRNA methyltransferase) regulates ANAPC4 expression as a downstream target: TRMT13 overexpression increases ANAPC4 levels, silencing of TRMT13 reduces ANAPC4 levels, and rescue experiments with ANAPC4 overexpression restore the anti-tumorigenic phenotype, placing ANAPC4 downstream of TRMT13 in papillary thyroid cancer cells. siRNA knockdown, overexpression, rescue experiments, nude mouse xenograft tumor model Acta biochimica et biophysica Sinica Medium 38425244
2024 ANAPC4 functions as a tumor suppressor in papillary thyroid cancer: loss-of-function (siRNA) promotes proliferation, migration and invasion, while overexpression inhibits tumor growth in a nude mouse xenograft model. siRNA knockdown, overexpression, cell proliferation/migration/invasion assays, nude mouse xenograft Acta biochimica et biophysica Sinica Medium 38425244
2021 An ANAPC4 E16K concurrent mutation (together with MFSD11 L242I) was associated with decreased trastuzumab sensitivity in BT-474 HER2-positive breast cancer cells, implicating ANAPC4 in drug resistance. Exome sequencing, single-cell targeted sequencing, validation of concurrent mutations by functional sensitivity assay Breast cancer research and treatment Low 33905021

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Y-box binding protein 1 is up-regulated in proliferative breast cancer and its inhibition deregulates the cell cycle. International journal of oncology 32 20596676
2015 Association between cell cycle gene transcription and tumor size in oral squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 26152289
2020 Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate. Oral diseases 14 33128317
2019 Transcriptome analysis revealed that aflatoxin M1 could cause cell cycle arrest in differentiated Caco-2 cells. Toxicology in vitro : an international journal published in association with BIBRA 13 30928695
2020 Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer. Methods and protocols 8 32899298
2023 Transcriptome Analysis of Reciprocal Hybrids Between Crassostrea gigas and C. angulata Reveals the Potential Mechanisms Underlying Thermo-Resistant Heterosis. Marine biotechnology (New York, N.Y.) 5 36653591
2024 TRMT13 inhibits the growth of papillary thyroid cancer by targeting ANAPC4. Acta biochimica et biophysica Sinica 4 38425244
2025 Air pollution exacerbates cardiovascular-kidney-metabolic syndrome and sarcopenia comorbidity via shared genetic-epigenetic mechanisms: A multi-omics and Mendelian Randomization study. Metabolism: clinical and experimental 3 41270966
2024 Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity. Frontiers in immunology 3 38633255
2021 Concurrent mutations associated with trastuzumab-resistance revealed by single cell sequencing. Breast cancer research and treatment 3 33905021
2025 Bayesian fine-mapping and Mendelian randomization leveraging expression quantitative trait loci reveal novel candidate causal genes for body conformation traits in cattle. Journal of dairy science 2 40383388
2024 Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis. Biomedicines 1 38927547
2026 Transcriptional Modulation of Infertility-Associated Genes Following Chlamydia trachomatis Infection in Human Fallopian Tube Mesenchymal Cells: In Silico Study. Genes 0 41898836
2025 PTTG1 as a common promising target for PCOS, Ovarian Cancer, and Major Depressive Disorder patients. Computational biology and chemistry 0 40925190
2025 Unraveling the shared genetic architecture of osteoarthritis and metabolic traits through multi-omics insights. Osteoarthritis and cartilage 0 41167325

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