ArticleProceedings of the National Academy of Sciences of the United States of America2017
Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate decisions under stressful conditions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Metallothionein 1X is a tumor suppressor gene and inhibits oxidative stress and metastasis in renal cell carcinoma.Discover oncology · 2025Article
- XAF1 is secreted from stressed tumor cells to activate T cell-mediated tumor surveillance via Lck-ERK signaling.Neoplasia (New York, N.Y.) · 2025Article
- XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy.Molecular biomedicine · 2024Article
- Near-infrared light responsive gold nanoparticles coating endows polyetheretherketone with enhanced osseointegration and antibacterial properties.Materials today. Bio · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma.Discover oncology · 2023Article
- Metallothionein-2A Protects Cardiomyocytes from Hypoxia/reper-Fusion through Inhibiting p38.Cell biochemistry and biophysics · 2023Article
- Blood RNA Sequencing Indicates UpregulatedInternational journal of molecular sciences · 2022Article
- Construction of miRNA-lncRNA-mRNA co-expression network affecting EMT-mediated cisplatin resistance in ovarian cancer.Journal of cellular and molecular medicine · 2022Article
- XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP.Cell death & disease · 2022Article
- Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification.Nucleic acids research · 2022Article
- Article
- Zinc ions negatively regulate proapoptotic signaling in cells expressing oncogenic mutant Ras.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC.Frontiers in immunology · 2022Article
- Functional Analysis of the Promoter Regions of Two Apoptosis-Related Genes (International journal of molecular sciences · 2021Article
- Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma.Frontiers in molecular biosciences · 2021Article
- XAF1 as a modifier of p53 function and cancer susceptibility.Science advances · 2020Article
- Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the transcriptome.Scientific reports · 2019Article
- XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis.Cell death & disease · 2018Article
- Cuproplasia-related gene signature: Prognostic insights for glioma therapy.Neuro-oncology advancesArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
XIAP-associated factor 1 (XAF1) is a tumor suppressor that is commonly inactivated in multiple human neoplasms. However, the molecular mechanism underlying its proapoptotic function remains largely undefined. Here, we report that XAF1 induction by heavy metals triggers an apoptotic switch of stress response by destabilizing metallothionein 2A (MT2A). XAF1 directly interacts with MT2A and facilitates its lysosomal degradation, resulting in the elevation of the free intercellular zinc level and subsequent activation of p53 and inactivation of XIAP. Intriguingly, XAF1 is activated as a unique transcription target of metal-regulatory transcription factor-1 (MTF-1) in signaling apoptosis, and its protein is destabilized via the lysosomal pathway by MTF-1-induced MT2A under cytostatic stress conditions, indicating the presence of mutual antagonism between XAF1 and MT2A. The antagonistic interplay between XAF1 and MT2A acts as a key molecular switch in MTF-1-mediated cell-fate decisions and also plays an important role in cell response to various apoptotic and survival factors. Wild-type (WT) XAF1 but not MT2A binding-deficient mutant XAF1 increases the free intracellular zinc level and accelerates WT folding of p53 and degradation of XIAP. Consistently, XAF1 evokes a more drastic apoptotic effect in
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