ArticleCell death & disease2013
Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to γ-radiation.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.Cell death & disease · 2025Article
- DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.Proteomes · 2025Article
- PP2C phosphatases-terminators of suicidal thoughts.Cell death & disease · 2024Review
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities.Experimental & molecular medicine · 2022Review
- MiR-145-5p Inhibits the Invasion of Prostate Cancer and Induces Apoptosis by Inhibiting WIP1.Journal of oncology · 2021Article
- Model-based optimization of combination protocols for irradiation-insensitive cancers.Scientific reports · 2020Article
- Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors.Journal of pathology and translational medicine · 2018Article
- JNK3 phosphorylates Bax protein and induces ability to form pore on bilayer lipid membrane.Biochimie open · 2017Article
- Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway.Molecular medicine reports · 2017Article
- WIP1 phosphatase as pharmacological target in cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Homeodomain-interacting protein kinase 2 (HIPK2): a promising target for anti-cancer therapies.Oncotarget · 2017Review
- LZAP is a novel Wip1 binding partner and positive regulator of its phosphatase activity in vitro.Cell cycle (Georgetown, Tex.) · 2017Article
- Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3.Oncotarget · 2016Article
- Direct Activation of Bax Protein for Cancer Therapy.Medicinal research reviews · 2016Review
- Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression.International journal of molecular sciences · 2015Article
- 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
- Downregulation of HIPK2 increases resistance of bladder cancer cell to cisplatin by regulating Wip1.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that switches off DNA damage checkpoint responses by the dephosphorylation of certain proteins (i.e. p38 mitogen-activated protein kinase, p53, checkpoint kinase 1, checkpoint kinase 2, and uracil DNA glycosylase) involved in DNA repair and the cell cycle checkpoint. Emerging data indicate that Wip1 is amplified or overexpressed in various human tumors, and its detection implies a poor prognosis. In this study, we show that Wip1 interacts with and dephosphorylates BAX to suppress BAX-mediated apoptosis in response to γ-irradiation in prostate cancer cells. Radiation-resistant LNCaP cells showed dramatic increases in Wip1 levels and impaired BAX movement to the mitochondria after γ-irradiation, and these effects were reverted by a Wip1 inhibitor. These results show that Wip1 directly interacts with and dephosphorylates BAX. Dephosphorylation occurs at threonines 172, 174 and 186, and BAX proteins with mutations at these sites fail to translocate efficiently to the mitochondria following cellular γ-irradiation. Overexpression of Wip1 and BAX, but not phosphatase-dead Wip1, in BAX-deficient cells strongly reduces apoptosis. Our results suggest that BAX dephosphorylation of Wip1 phosphatase is an important regulator of resistance to anticancer therapy. This study is the first to report the downregulation of BAX activity by a protein phosphatase.
Indexed as
Identifiers
What OpenQuestion holds
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.