ArticleOncogene2012
Hypoxic activation of ATR and the suppression of the initiation of DNA replication through cdc6 degradation.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- Claspin-Dependent and -Independent Chk1 Activation by a Panel of Biological Stresses.Biomolecules · 2023Article
- Epigenetic Reprogramming of Kaposi's Sarcoma-Associated Herpesvirus during Hypoxic Reactivation.Cancers · 2022Article
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- HIF1α-Regulated Expression of the Fatty Acid Binding Protein Family Is Important for Hypoxic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus.Journal of virology · 2021Article
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- Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations.Cancer research · 2014Article
- The circadian clock and the hypoxic response pathway in kidney cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.Oncogene · 2013Article
- A nontranscriptional role for HIF-1α as a direct inhibitor of DNA replication.Science signaling · 2013Article
- Targeting radiation-resistant hypoxic tumour cells through ATR inhibition.British journal of cancer · 2012Article
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Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Many severely hypoxic cells fail to initiate DNA replication, but the mechanism underlying this observation is unknown. Specifically, although the ataxia-telangiectasia-rad3 related (ATR) kinase has been shown to be activated in hypoxic cells, several studies have not been able to document down-stream consequences of ATR activation in these cells. By clearly defining the DNA replication initiation checkpoint in hypoxic cells, we now demonstrate that ATR is responsible for activating this checkpoint. We show that the hypoxic activation of ATR leads to the phosphorylation-dependent degradation of the cdc25a phosphatase. Downregulation of cdc25a protein by ATR in hypoxic cells decreases CDK2 phosphorylation and activity, which results in the degradation of cdc6 by APC/C(Cdh1). These events do not occur in hypoxic cells when ATR is depleted, and the initiation of DNA replication is maintained. We therefore present a novel mechanism of cdc6 regulation in which ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of cdc6 by APC/C(Cdh1). This model provides insight into the biology and therapy of hypoxic tumors.
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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.