ArticleProceedings of the National Academy of Sciences of the United States of America2014
XAF1 directs apoptotic switch of p53 signaling through activation of HIPK2 and ZNF313.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- RASSF4 Suppresses Gastric Tumor Growth through Activation of Chk2-p53 Signaling Axis.Cancer research and treatment · 2026Article
- SLC7A8 is essential for metabolic fitness and function of Th2 cells.The Journal of experimental medicine · 2026Article
- The molecular mechanisms and therapeutic potential of p53 in kidney injury repair: a perspective on the p53alpha/delta133p53alpha signaling axis.Renal failure · 2025Review
- The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research.Journal of translational medicine · 2025Review
- Review
- The multifunctional proline-rich domain of p53 tumor suppressor.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Junction Plakoglobin - A Dual-Role Player in Cancer Biology.International journal of surgery (London, England) · 2025Review
- 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
- STAT3 protects hematopoietic stem cells by preventing activation of a deleterious autocrine type-I interferon response.Leukemia · 2024Article
- XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.The Journal of cell biology · 2024Article
- Interferon alpha promotes caspase-8 dependent ultraviolet light-mediated keratinocyte apoptosis via interferon regulatory factor 1.Frontiers in immunology · 2024Article
- Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality inScience advances · 2023Article
- Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity inBiomedicines · 2023Article
- Recognition of Differentially Expressed Molecular Signatures and Pathways Associated with COVID-19 Poor Prognosis in Glioblastoma Patients.International journal of molecular sciences · 2023Article
- Immunogenomic profile at baseline predicts host susceptibility to clinical malaria.Frontiers in immunology · 2023Article
- XAF1 overexpression exacerbates diabetes by promoting pancreatic β-cell apoptosis.Acta diabetologica · 2022Article
- XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.Journal of virology · 2022Article
- METTL14-dependent mCell reports · 2022Article
- Construction of miRNA-lncRNA-mRNA co-expression network affecting EMT-mediated cisplatin resistance in ovarian cancer.Journal of cellular and molecular medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a tumor suppressor that is frequently inactivated in many human cancers. However, the molecular mechanism underlying its growth-inhibitory function remains largely unknown. Here, we report that XAF1 forms a positive feedback loop with p53 and acts as a molecular switch in p53-mediated cell-fate decisions favoring apoptosis over cell-cycle arrest. XAF1 binds directly to the N-terminal proline-rich domain of p53 and thus interferes with E3 ubiquitin ligase MDM2 binding and ubiquitination of p53. XAF1 stimulates homeodomain-interacting protein kinase 2 (HIPK2)-mediated Ser-46 phosphorylation of p53 by blocking E3 ubiquitin ligase Siah2 interaction with and ubiquitination of HIPK2. XAF1 also steps up the termination of p53-mediated cell-cycle arrest by activating zinc finger protein 313 (ZNF313), a p21(WAF1)-targeting ubiquitin E3 ligase. XAF1 interacts with p53, Siah2, and ZNF313 through the zinc finger domains 5, 6, and 7, respectively, and truncated XAF1 isoforms preferentially expressed in cancer cells fail to form a feedback loop with p53. Together, this study uncovers a novel role for XAF1 in p53 stress response, adding a new layer of complexity to the mechanisms by which p53 determines cell-fate decisions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.