ArticleCellular and molecular life sciences : CMLS2015
A kinome-targeted RNAi-based screen links FGF signaling to H2AX phosphorylation in response to radiation.
Article in Cellular and molecular life sciences : CMLS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Adverse effects of ovarian cryopreservation and auto-transplantation on ovarian grafts and quality of produced oocytes in a mouse model.Clinical science (London, England : 1979) · 2023Article
- FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas.Molecular oncology · 2022Article
- A High-throughput Approach to Identify Effective Systemic Agents for the Treatment of Anaplastic Thyroid Carcinoma.The Journal of clinical endocrinology and metabolism · 2021Article
- Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress.The EMBO journal · 2021Article
- Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens.Nucleic acids research · 2018Article
- Oxidative Stress Delays Prometaphase/Metaphase of the First Cleavage in Mouse Zygotes via the MAD2L1-Mediated Spindle Assembly Checkpoint.Oxidative medicine and cellular longevity · 2017Article
- Oxidative stress-induced DNA damage of mouse zygotes triggers G2/M checkpoint and phosphorylates Cdc25 and Cdc2.Cell stress & chaperones · 2016Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A general radioprotective effect by fibroblast growth factor (FGF) has been extensively described since the early 1990s; however, the molecular mechanisms involved remain largely unknown. Radiation-induced DNA double-strand breaks (DSBs) lead to a complex set of responses in eukaryotic cells. One of the earliest consequences is phosphorylation of histone H2AX to form nuclear foci of the phosphorylated form of H2AX (γH2AX) in the chromatin adjacent to sites of DSBs and to initiate the recruitment of DNA-repair molecules. Upon a DSB event, a rapid signaling network is activated to coordinate DNA repair with the induction of cell-cycle checkpoints. To date, three kinases (ATM, ATR, and DNA-PK) have been shown to phosphorylate histone H2AX in response to irradiation. Here, we report a kinome-targeted small interfering RNA (siRNA) screen to characterize human kinases involved in H2AX phosphorylation. By analyzing γH2AX foci at a single-nucleus level, we identified 46 kinases involved either directly or indirectly in H2AX phosphorylation in response to irradiation in human keratinocytes. Furthermore, we demonstrate that in response to irradiation, the FGFR4 signaling cascade promotes JNK1 activation and direct H2AX phosphorylation leading, in turn, to more efficient DNA repair. This can explain, at least partially, the radioprotective effect of FGF.
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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.