ArticleEMBO molecular medicine2012
Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence.
Article in EMBO molecular medicine, 2012. 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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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
21 citing papers in PubMed, 29 citations in OpenAlex.
- PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- PML Body Biogenesis: A Delicate Balance of Interactions.International journal of molecular sciences · 2023Review
- Article
- Deregulated PP1α phosphatase activity towards MAPK activation is antagonized by a tumor suppressive failsafe mechanism.Nature communications · 2018Article
- PML: Regulation and multifaceted function beyond tumor suppression.Cell & bioscience · 2018Review
- PML is a ROS sensor activating p53 upon oxidative stress.The Journal of experimental medicine · 2017Article
- The DNA repair function of CUX1 contributes to radioresistance.Oncotarget · 2017Article
- Focal Adhesion Kinase Regulates the DNA Damage Response and Its Inhibition Radiosensitizes Mutant KRAS Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- The Fanconi anemia pathway controls oncogenic response in hematopoietic stem and progenitor cells by regulating PRMT5-mediated p53 arginine methylation.Oncotarget · 2016Article
- Translational control of PML contributes to TNFα-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs.Cell death and differentiation · 2016Article
- MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition.Oncotarget · 2015Article
- The function, regulation and therapeutic implications of the tumor suppressor protein, PML.Cell & bioscience · 2015Review
- Computational image analysis of colony and nuclear morphology to evaluate human induced pluripotent stem cells.Scientific reports · 2014Article
- PML-mediated signaling and its role in cancer stem cells.Oncogene · 2014Review
- RAS transformation requires CUX1-dependent repair of oxidative DNA damage.PLoS biology · 2014Article
- Cellular senescence and protein degradation: breaking down cancer.Cell cycle (Georgetown, Tex.) · 2014Article
- PML Surfs into HIPPO Tumor Suppressor Pathway.Frontiers in oncology · 2013Article
- PML Degradation: Multiple Ways to Eliminate PML.Frontiers in oncology · 2013Article
- PML: Not all about Tumor Suppression.Frontiers in oncology · 2013Article
- PML, SUMOylation, and Senescence.Frontiers in oncology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Expression of oncogenic K-RAS in primary cells elicits oncogene-induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms that depend on the p53 tumour suppressor protein. The PML tumour suppressor was initially identified as a component of the PML-RARα oncoprotein of acute promyelocytic leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K-RAS in vivo and in vitro. We demonstrate here that oncogenic K-RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53. Under these circumstances, PML mRNA is selectively associated to polysomes. Importantly, we find that the PML 5' untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response. These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K-RAS-induced OIS. Thus, selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL.
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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.