ArticleThe EMBO journal2006
ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 162 citations in OpenAlex.
- The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability.Nature communications · 2026Article
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- Laminaria japonica Polysaccharide Alleviates Radiation-Induced Salivary Gland Injury by Promoting DNA Damage Repair.International dental journal · 2026Article
- Molecular Drivers of Chromophobe Renal Cell Carcinoma Revealed Through Genomic Analysis Using AACR Project GENIE.Life (Basel, Switzerland) · 2025Article
- Mapping the current research landscape of metformin in cancer based on bibliometric analysis.Discover oncology · 2025Article
- ATM and p53 in aging and cancer: a double-edged sword in genomic integrity.Biogerontology · 2025Review
- Oncogenic activation of SMYD3-SHCBP1 promotes breast cancer development and is coupled with resistance to immune therapy.Cell death & disease · 2025Article
- BRCA1 is involved in sustaining rapid antler growth possibly via balancing of the p53/endoplasmic reticulum stress signaling pathway.Biology direct · 2025Article
- Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target.Genes & diseases · 2025Review
- Manganese mediates antiviral effects by driving an ATM -TBK1 phosphorylation signaling pathway.Frontiers in immunology · 2025Article
- Unraveling the nexus between cellular senescence and malignant transformation: a paradigm shift in cancer research.Cancer biology & medicine · 2024Article
- Identification and clinicopathological analysis of potential p73-regulated biomarkers in colorectal cancer via integrative bioinformatics.Scientific reports · 2024Article
- ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance.Cell death & disease · 2024Article
- Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.BMC cancer · 2024Article
- Regulated secretion of mutant p53 negatively affects T lymphocytes in the tumor microenvironment.Oncogene · 2024Article
- Brca1 Mouse Models: Functional Insights and Therapeutic Opportunities.Journal of molecular biology · 2024Review
- Article
- BRCA1 Insufficiency Induces a Hypersialylated Acidic Tumor Microenvironment That Promotes Metastasis and Immunotherapy Resistance.Cancer research · 2023Article
- Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling.Science advances · 2023Article
- Phenethyl isothiocyanate and dasatinib combination synergistically reduces hepatocellular carcinoma growth via cell cycle arrest and oxeiptosis.Frontiers in pharmacology · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
BRCA1 is a checkpoint and DNA damage repair gene that secures genome integrity. We have previously shown that mice lacking full-length Brca1 (Brca1(delta11/delta11)) die during embryonic development. Haploid loss of p53 completely rescues embryonic lethality, and adult Brca1(delta11/delta11)p53+/- mice display cancer susceptibility and premature aging. Here, we show that reduced expression and/or the absence of Chk2 allow Brca1(delta11/delta11) mice to escape from embryonic lethality. Compared to Brca1(delta11/delta11)p53+/- mice, lifespan of Brca1(delta11/delta11)Chk2-/- mice was remarkably extended. Analysis of Brca1(delta11/delta11)Chk2-/- mice revealed that p53-dependent apoptosis and growth defect caused by Brca1 deficiency are significantly attenuated in rapidly proliferating organs. However, in later life, Brca1(delta11/delta11)Chk2-/- female mice developed multiple tumors. Furthermore, haploid loss of ATM also rescued Brca1 deficiency-associated embryonic lethality and premature aging. Thus, in response to Brca1 deficiency, the activation of the ATM-Chk2-p53 signaling pathway contributes to the suppression of neoplastic transformation, while leading to compromised organismal homeostasis. Our data highlight how accurate maintenance of genomic integrity is critical for the suppression of both aging and malignancy, and provide a further link between aging and cancer.
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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.