ArticleCell cycle (Georgetown, Tex.)2014
Rho GTPase independent regulation of ATM activation and cell survival by the RhoGEF Net1A.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- NET1 is a critical regulator of spindle assembly and actin dynamics in mouse oocytes.Reproductive biology and endocrinology : RB&E · 2024Article
- MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of NuclearMolecular and cellular biology · 2024Article
- A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells.BMC complementary medicine and therapies · 2021Article
- Cdk1 phosphorylation negatively regulates the activity of Net1 towards RhoA during mitosis.Cellular signalling · 2021Article
- Role of Small GTPase RhoA in DNA Damage Response.Biomolecules · 2021Review
- HIF2 Regulates Intestinal Wnt5a Expression.Frontiers in oncology · 2021Article
- Rho GTPases in cancer radiotherapy and metastasis.Cancer metastasis reviews · 2020Review
- Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
ATM activation following DNA damage is a critical event which is required for efficient DNA repair and cell survival, yet signaling mechanisms controlling its activation are incompletely understood. The RhoGEF Net1 has previously been reported to control Rho GTPase activation and downstream cell survival outcomes following double strand DNA damage. However the role of Net1 isoforms in controlling ATM-dependent cell signaling has not been assessed. In the present work we show that expression of the Net1A isoform is specifically required for efficient activation of ATM but not the related kinase DNA-PK after ionizing radiation. Surprisingly Net1A overexpression also potently suppresses ATM activation and phosphorylation of its substrate H2AX. This effect does not require catalytic activity towards RhoA or RhoB, and neither Rho GTPase affects ATM activation, on its own. Consistent with a role in controlling ATM activation, Net1A knockdown also impairs DNA repair and cell survival. Taken together these data indicate that Net1A plays a plays a previously unrecognized, Rho GTPase-independent role in controlling ATM activity and downstream signaling after DNA damage to impact cell 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.