ArticleNature chemical biology2012
ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
46 citing papers in PubMed, 68 citations in OpenAlex.
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Understanding the complexity of p53 in a new era of tumor suppression.Cancer cell · 2024Review
- Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway.Cancer research · 2023Article
- P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway.Nucleic acids research · 2023Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Transcriptional Silencing ofCancer discovery · 2021Article
- Role of mTOR As an Essential Kinase in SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2020Article
- Identification of universal and cell-type specific p53 DNA binding.BMC molecular and cell biology · 2020Article
- Inhibition of p53 inhibitors: progress, challenges and perspectives.Journal of molecular cell biology · 2019Review
- Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy.Science advances · 2019Article
- Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors.Cell reports · 2017Article
- Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity.Genome research · 2017Article
- A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response.Molecular and cellular biology · 2017Article
- A Genome-Wide Loss-of-Function Screen Identifies SLC26A2 as a Novel Mediator of TRAIL Resistance.Molecular cancer research : MCR · 2017Article
- SMYD2 lysine methyltransferase regulates leukemia cell growth and regeneration after genotoxic stress.Oncotarget · 2017Article
- CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations.Molecular cell · 2016Article
- p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity.Nature medicine · 2016Article
- Article
- The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression.Cold Spring Harbor perspectives in medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The p53 tumor suppressor orchestrates alternative stress responses including cell cycle arrest and apoptosis, but the mechanisms defining cell fate upon p53 activation are poorly understood. Several small-molecule activators of p53 have been developed, including Nutlin-3, but their therapeutic potential is limited by the fact that they induce reversible cell cycle arrest in most cancer cell types. We report here the results of a genome-wide short hairpin RNA screen for genes that are lethal in combination with p53 activation by Nutlin-3, which showed that the ATM and MET kinases govern cell fate choice upon p53 activation. Genetic or pharmacological interference with ATM or MET activity converts the cellular response from cell cycle arrest into apoptosis in diverse cancer cell types without affecting expression of key p53 target genes. ATM and MET inhibitors also enable Nutlin-3 to kill tumor spheroids. These results identify new pathways controlling the cellular response to p53 activation and aid in the design of p53-based therapies.
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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.