ArticleMolecular cell2015
ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 97 citations in OpenAlex.
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Review
- A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC.Cancer letters · 2025Article
- A tethering mechanism underlies Pin1-catalyzed prolineProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- ATR regulates OCT4 phosphorylation and safeguards human naïve pluripotency.Scientific reports · 2025Article
- Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein.Cancer communications (London, England) · 2025Article
- DNA damage response regulator ATR licenses PINK1-mediated mitophagy.Nucleic acids research · 2025Article
- Multiple entanglements of different cell death pathways, in which caspase-8 and BID interact with cardiolipin*, have been identified.Frontiers in cell and developmental biology · 2025Review
- Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A novel role for the peptidyl-prolyl cis-trans isomerase Cyclophilin A in DNA-repair following replication fork stalling via the MRE11-RAD50-NBS1 complex.EMBO reports · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Protein expression of nucleolar protein 12 in the retina and its implication in protection of retina from UV irradiation damage.Cell death discovery · 2024Article
- Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment.DNA repair · 2023Article
- Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.International journal of molecular sciences · 2023Review
- Review
- Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma.International journal of molecular sciences · 2023Review
- Exploiting Multi-Omics Profiling and Systems Biology to Investigate Functions of TOMM34.Biology · 2023Article
- Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Advances in biological regulation · 2023Article
- Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
ATR, a PI3K-like protein kinase, plays a key role in regulating DNA damage responses. Its nuclear checkpoint kinase function is well documented, but little is known about its function outside the nucleus. Here we report that ATR has an antiapoptotic activity at mitochondria in response to UV damage, and this activity is independent of its hallmark checkpoint/kinase activity and partner ATRIP. ATR contains a BH3-like domain that allows ATR-tBid interaction at mitochondria, suppressing cytochrome c release and apoptosis. This mitochondrial activity of ATR is downregulated by Pin1 that isomerizes ATR from cis-isomer to trans-isomer at the phosphorylated Ser428-Pro429 motif. However, UV inactivates Pin1 via DAPK1, stabilizing the pro-survival cis-isomeric ATR. In contrast, nuclear ATR remains in the trans-isoform disregarding UV. This cytoplasmic response of ATR may provide a mechanism for the observed antiapoptotic role of ATR in suppressing carcinogenesis and its inhibition in sensitizing anticancer agents for killing of cancer cells.
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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.