ArticleMolecular cell2013
A posttranslational modification cascade involving p38, Tip60, and PRAK mediates oncogene-induced senescence.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- DUSP4 activates adipocyte thermogenesis via CRTC3 dephosphorylation-dependent UCP1 expression.Experimental & molecular medicine · 2026Article
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- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Post-translational modifications of epigenetic modifier TIP60: their role in cellular functions and cancer.Epigenetics & chromatin · 2025Review
- Review
- Transcriptome Profiling of Mouse Embryonic Fibroblast Spontaneous Immortalization: A Comparative Analysis.International journal of molecular sciences · 2024Article
- NOS2 andProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Recruitment of KMT2C/MLL3 to DNA Damage Sites Mediates DNA Damage Responses and Regulates PARP Inhibitor Sensitivity in Cancer.Cancer research · 2021Article
- Article
- KAT5 acetylates cGAS to promote innate immune response to DNA virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Requirement for epithelial p38α in KRAS-driven lung tumor progression.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Research · 2020Review
- DNA damage response manages cell cycle restriction of senile multipotent mesenchymal stromal cells.Molecular biology reports · 2020Review
- Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.Nature communications · 2018Article
- Tip60: updates.Journal of applied genetics · 2018Review
- CDK9-mediated phosphorylation controls the interaction of TIP60 with the transcriptional machinery.EMBO reports · 2018Article
- Acetylation of TIP60 at K104 is essential for metabolic stress-induced apoptosis in cells of hepatocellular cancer.Experimental cell research · 2018Article
- E3 ligase EDD1/UBR5 is utilized by the HPV E6 oncogene to destabilize tumor suppressor TIP60.Oncogene · 2016Article
- Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.PLoS pathogens · 2015Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Oncogene-induced senescence is an important tumor-suppressing defense mechanism. However, relatively little is known about the signaling pathway mediating the senescence response. Here, we demonstrate that a multifunctional acetyltransferase, Tip60, plays an essential role in oncogenic ras-induced senescence. Further investigation reveals a cascade of posttranslational modifications involving p38, Tip60, and PRAK, three proteins that are essential for ras-induced senescence. Upon activation by ras, p38 induces the acetyltransferase activity of Tip60 through phosphorylation of Thr158; activated Tip60 in turn directly interacts with and induces the protein kinase activity of PRAK through acetylation of K364 in a manner that depends on phosphorylation of both Tip60 and PRAK by p38. These posttranslational modifications are critical for the prosenescent function of Tip60 and PRAK, respectively. These results have defined a signaling pathway that mediates oncogene-induced senescence, and identified posttranslational modifications that regulate the enzymatic activity and biological functions of Tip60 and PRAK.
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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.