ArticleCell cycle (Georgetown, Tex.)2012
Wip1 sensitizes p53-negative tumors to apoptosis by regulating the Bax/Bcl-xL ratio.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease.Scientific reports · 2025Article
- PP2C phosphatases-terminators of suicidal thoughts.Cell death & disease · 2024Review
- Discovery of Novel Small-Molecule Scaffolds for the Inhibition and Activation of WIP1 Phosphatase from a RapidFire Mass Spectrometry High-Throughput Screen.ACS pharmacology & translational science · 2022Article
- Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.The Journal of biological chemistry · 2019Article
- Role of wild-type p53-induced phosphatase 1 in cancer.Oncology letters · 2017Article
- WIP1 phosphatase as pharmacological target in cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway.Molecular medicine reports · 2017Article
- DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system and inflammation.Cell death discovery · 2017Review
- Wip1 phosphatase: between p53 and MAPK kinases pathways.Oncotarget · 2016Review
- Wip1 suppresses ovarian cancer metastasis through the ATM/AKT/Snail mediated signaling.Oncotarget · 2016Article
- Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy.Cell death & disease · 2016Article
- Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3.Oncotarget · 2016Article
- Wip1 phosphatase in breast cancer.Oncogene · 2015Review
- WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to γ-radiation.Cell death & disease · 2013Article
- p53 and Ceramide as Collaborators in the Stress Response.International journal of molecular sciences · 2013Article
- INMAP, a novel truncated version of POLR3B, represses AP-1 and p53 transcriptional activity.Molecular and cellular biochemistry · 2013Article
- Garcinol Alone and in Combination With Cisplatin Affect Cellular Behavior and PI3K/AKT Protein Phosphorylation in Human Ovarian Cancer Cells.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 3 countries.
Funding
Abstract
Wip1 is a stress-response phosphatase that negatively regulates several tumor suppressors, including p53. In a sizeable fraction of tumors, overexpression or amplification of Wip1 compromises p53 functions; inhibition of Wip1 activity is an attractive strategy for improving treatment of these tumors. However, over half of human tumors contain mutations in the p53 gene or have lost both alleles. Recently, we observed that in cancer cells lacking wild type p53, reduction of Wip1 expression was ineffective, whereas, surprisingly, overexpression of Wip1 increased anticancer drug sensitivity. The increased sensitivity resulted from activation of the intrinsic pathway of apoptosis through increased levels of the pro-apoptotic protein Bax and decreased levels of the anti-apoptotic protein Bcl-xL. We showed that interaction of Wip1 and the transcription factor RUNX2, specifically through dephosphorylation of RUNX2 phospho-S432, resulted in increased expression of Bax. Interestingly, overexpression of Wip1 increased drug sensitivity only in the p53-negative tumor cells while protecting the wild type p53-containing normal cells from drug-induced collateral injury. Here, we provide evidence that Wip1 overexpression decreases expression of Bcl-xL through negative regulation of NFκB activity. Thus, Wip1 overexpression increases the sensitivity of p53-negative cancer cells to anticancer drugs by separately affecting Bax and Bcl-xL protein levels.
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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.