ArticleCancer research2012
A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies.Molecular biology reports · 2014Pooled it
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- ATR-hippo drives force signaling to nuclear F-actin and links mechanotransduction to neurological disorders.Science advances · 2025Article
- Explainable machine learning predicts survival of retroperitoneal liposarcoma: A study based on the SEER database and external validation in China.Cancer medicine · 2024Article
- New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.Cancers · 2023Review
- The Hippo signaling pathway: from multiple signals to the hallmarks of cancers.Acta biochimica et biophysica Sinica · 2023Review
- Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers.The Journal of clinical investigation · 2022Article
- Is Autophagy Always a Barrier to Cisplatin Therapy?Biomolecules · 2022Review
- Review
- The Role and Function of Ras-association domain family in Cancer: A Review.Genes & diseases · 2019Review
- RASSF1A controls tissue stiffness and cancer stem-like cells in lung adenocarcinoma.The EMBO journal · 2019Article
- The Ambivalent Function of YAP in Apoptosis and Cancer.International journal of molecular sciences · 2018Review
- MST2 kinase suppresses rDNA transcription in response to DNA damage by phosphorylating nucleolar histone H2B.The EMBO journal · 2018Article
- Tumor suppressor C-RASSF proteins.Cellular and molecular life sciences : CMLS · 2018Review
- p53 shades of Hippo.Cell death and differentiation · 2018Review
- The tumor suppressor RASSF1A induces the YAP1 target geneOncotarget · 2017Article
- Functions and Epigenetic Regulation of Wwox in Bone Metastasis from Breast Carcinoma: Comparison with Primary Tumors.International journal of molecular sciences · 2017Review
- Ras signaling through RASSF proteins.Seminars in cell & developmental biology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
RASSF1A (Ras association domain containing family 1A), a tumor suppressor gene that is frequently inactivated in human cancers, is phosphorylated by ataxia telangiectasia mutated (ATM) on Ser131 upon DNA damage, leading to activation of a p73-dependent apoptotic response. A single-nucleotide polymorphism located in the region of the key ATM activation site of RASSF1A predicts the conversion of alanine (encoded by the major G allele) to serine (encoded by the minor T allele) at residue 133 of RASSF1A (p.Ala133Ser). Secondary protein structure prediction studies suggest that an alpha helix containing the ATM recognition site is disrupted in the serine isoform of RASSF1A (RASSF1A-p.133Ser). In this study, we observed a reduced ability of ATM to recruit and phosphorylate RASSF1A-p.133Ser upon DNA damage. RASSF1A-p.133Ser failed to activate the MST2/LATS pathway, which is required for YAP/p73-mediated apoptosis, and negatively affected the activation of p53, culminating in a defective cellular response to DNA damage. Consistent with a defective p53 response, we found that male soft tissue sarcoma patients carrying the minor T allele encoding RASSF1A-p.133Ser exhibited poorer tumor-specific survival and earlier age of onset compared with patients homozygous for the major G allele. Our findings propose a model that suggests a certain subset of the population have inherently weaker p73/p53 activation due to inefficient signaling through RASSF1A, which affects both cancer incidence and survival.
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Registered trials
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.