ArticleCancer biology & therapy2014
Enhancement of cellular radiation sensitivity through degradation of Chk1 by the XIAP-XAF1 complex.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.International journal of molecular sciences · 2024Article
- A ceRNA regulatory network in systemic lupus erythematosus and its molecular interplay with cancer.Annals of translational medicine · 2022Article
- Cytoplasmic and Nuclear Functions of cIAP1.Biomolecules · 2022Review
- Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection.Viruses · 2021Article
- [Effect of stable overexpression of XAF1 gene on biological characteristics of ovarian cancer A2780 cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Identification of Key Genes Mutations Associated With the Radiosensitivity by Whole Exome Sequencing in Pancreatic Cancer.Frontiers in oncology · 2021Article
- Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells.Journal of experimental & clinical cancer research : CR · 2020Article
- Review
- Kinome expression profiling to target new therapeutic avenues in multiple myeloma.Haematologica · 2020Article
- Paradoxical epigenetic regulation of XAF1 mediates plasticity towards adaptive resistance evolution in MGMT-methylated glioblastoma.Scientific reports · 2019Article
- SPOP regulates the DNA damage response and lung adenocarcinoma cell response to radiation.American journal of cancer research · 2019Article
- Epigenetic silencing of XAF1 in high-grade gliomas is associated with IDH1 status and improved clinical outcome.Oncotarget · 2017Article
- Lack of Casein Kinase 1 Delta Promotes Genomic Instability - The Accumulation of DNA Damage and Down-Regulation of Checkpoint Kinase 1.PloS one · 2017Article
- A novel Chk1-binding peptide that enhances genotoxic sensitivity through the cellular redistribution of nuclear Chk1.International journal of molecular medicine · 2016Article
- Aberrant splicing and drug resistance in AML.Journal of hematology & oncology · 2016Review
- Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked inhibitor of apoptosis (XIAP) and Chk1 are potential molecular targets in radiotherapy. However, their molecular association in the regulation of radiation sensitivity has been rarely studied. Here, we show that XIAP modulates radiation sensitivity by regulating stability of Chk1 in lung cancer cells. Both Chk1 and XIAP are highly expressed in various lung cancer cells. Overexpression of XIAP increased cell survival following genotoxic treatments by preventing downregulation of Chk1. However, XIAP reversed Chk1-protective activity in the presence of XIAP-associated factor 1 (XAF1) by degrading Chk1 via ubiquitination-dependent proteasomal proteolysis. The XIAP-XAF1 complex-mediated Chk1 degradation also required CUL4A and DDB1. Chk1 or XIAP was associated with DDB1 and CUL4A. Depletion of CUL4A or DDB1 prevented the XIAP-XAF1-mediated Chk1 degradation suggesting involvement of a CUL4A/DDB1-based E3 ubiquitin ligase in the process or its collaboration with XIAP E3 ligase activity. Taken together, our findings show that XIAP plays a dual role in modulation of Chk1 stability and cell viability following IR. In the absence of XAF1, XIAP stabilizes Chk1 under IR with corresponding increase of cell viability. By contrast, when XAF1 is overexpressed, XIAP facilitates Chk1 degradation, which leads to enhancement of radiation sensitivity. This selective regulation of Chk1 stability by XIAP and XAF1 could be harnessed to devise a strategy to modulate radiation sensitivity in lung 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.