ArticleThe Journal of biological chemistry2014
p53 protein regulates Hsp90 ATPase activity and thereby Wnt signaling by modulating Aha1 expression.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- The Antifungal Activity of Loquat (Frontiers in nutrition · 2021Article
- Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link.International journal of obesity (2005) · 2018Article
- Regulation of the Tumor-Suppressor BECLIN 1 by Distinct Ubiquitination Cascades.International journal of molecular sciences · 2017Review
- The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head.Oncotarget · 2017Article
- Hsp90 activator Aha1 drives production of pathological tau aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hsp90 and PKM2 Drive the Expression of Aromatase in Li-Fraumeni Syndrome Breast Adipose Stromal Cells.The Journal of biological chemistry · 2016Article
- Targeting cancer stem cells with p53 modulators.Oncotarget · 2016Article
- Loss of p53 expression is accompanied by upregulation of beta-catenin in meningiomas: a concomitant reciprocal expression.International journal of experimental pathology · 2016Article
- HSP90AB1: Helping the good and the bad.Gene · 2016Review
- [Clinical significance of abnormal Wnt signaling pathway expression in hepatitis and hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2015Article
- Heat shock proteins: a therapeutic target worth to consider.Veterinary world · 2015Review
- Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases.Immunity & ageing : I & A · 2015Review
- A proteomic study of the differential protein expression in MDBK cells after bovine herpesvirus type 1 infection (BHV-1) strain treatment.International journal of clinical and experimental medicine · 2015Article
- Hsp90, the concertmaster: tuning transcription.Frontiers in oncology · 2015Review
- Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO.Cancers · 2014Review
- Mutation of essential Hsp90 co-chaperones SGT1 or CNS1 renders yeast hypersensitive to overexpression of other co-chaperones.Current genetics · 2014Article
- p53 modulates Hsp90 ATPase activity and regulates aryl hydrocarbon receptor signaling.Cancer prevention research (Philadelphia, Pa.) · 2014Article
Corrections and comments
- Retraction · 2019-12-02Duplication of/in Image · Manipulation of Images · · Dannenberg retired March 2021 - http://medicine.weill.cornell.edu/sites/default/files/wnim_2021-03.pdf
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- Retracted
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The p53 tumor suppressor gene encodes a homotetrameric transcription factor which is activated in response to a variety of cellular stressors, including DNA damage and oncogene activation. p53 mutations occur in >50% of human cancers. Although p53 has been shown to regulate Wnt signaling, the underlying mechanisms are not well understood. Here we show that silencing p53 in colon cancer cells led to increased expression of Aha1, a co-chaperone of Hsp90. Heat shock factor-1 was important for mediating the changes in Aha1 levels. Increased Aha1 levels were associated with enhanced interactions with Hsp90, resulting in increased Hsp90 ATPase activity. Moreover, increased Hsp90 ATPase activity resulted in increased phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β), leading to enhanced expression of Wnt target genes. Significantly, levels of Aha1, Hsp90 ATPase activity, Akt, and GSK3β phosphorylation and expression of Wnt target genes were increased in the colons of p53-null as compared with p53 wild type mice. Using p53 heterozygous mutant epithelial cells from Li-Fraumeni syndrome patients, we show that a monoallelic mutation of p53 was sufficient to activate the Aha1/Hsp90 ATPase axis leading to stimulation of Wnt signaling and increased expression of Wnt target genes. Pharmacologic intervention with CP-31398, a p53 rescue agent, inhibited recruitment of Aha1 to Hsp90 and suppressed Wnt-mediated gene expression in colon cancer cells. Taken together, this study provides new insights into the mechanism by which p53 regulates Wnt signaling and raises the intriguing possibility that p53 status may affect the efficacy of anticancer therapies targeting Hsp90 ATPase.
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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.