ArticleThe Journal of biological chemistry2010
Akt-phosphorylated mitogen-activated kinase-activating death domain protein (MADD) inhibits TRAIL-induced apoptosis by blocking Fas-associated death domain (FADD) association with death receptor 4.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- IG20/MADD gene functional isoform KIAA0358 can promote insulin secretion in glucose and repaglinide-induced pancreatic β-cells.Acta pharmacologica Sinica · 2026Article
- CRISPR/Cas9-mediated deletion of MADD induces cell cycle arrest and apoptosis in anaplastic thyroid cancer cells.Scientific reports · 2025Article
- The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases.Neuro-oncology · 2025Article
- Upregulation of exosome secretion from tumor-associated macrophages plays a key role in the suppression of anti-tumor immunity.Cell reports · 2023Article
- Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity.Cell genomics · 2023Article
- Review
- Advanced age exacerbates intestinal epithelial permeability after burn injury in mice.Experimental gerontology · 2022Article
- Vemurafenib may overcome TNF-related apoptosis-inducing ligand (TRAIL) resistance in anaplastic thyroid cancer cells.Endocrine · 2020Article
- Loss of MADD expression inhibits cellular growth and metastasis in anaplastic thyroid cancer.Cell death & disease · 2019Article
- Adult Hepatocytes Are Hedgehog-Responsive Cells in the Setting of Liver Injury: Evidence for Smoothened-Mediated Activation of NF-κB/Epidermal Growth Factor Receptor/Akt in Hepatocytes that Counteract Fas-Induced Apoptosis.The American journal of pathology · 2018Article
- Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra.Current genomics · 2017Review
- miR-223 Deficiency Protects against Fas-Induced Hepatocyte Apoptosis and Liver Injury through Targeting Insulin-Like Growth Factor 1 Receptor.The American journal of pathology · 2015Article
- 2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL.International journal of clinical and experimental pathology · 2015Article
- miR-150 Deficiency Protects against FAS-Induced Acute Liver Injury in Mice through Regulation of AKT.PloS one · 2015Article
- Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells.Neural regeneration research · 2014Article
- Article
- MADD is a downstream target of PTEN in triggering apoptosis.Journal of cellular biochemistry · 2014Article
- Resistance to TRAIL in non-transformed cells is due to multiple redundant pathways.Cell death & disease · 2013Article
- Down-modulation of expression, or dephosphorylation, of IG20/MADD in tumor necrosis factor-related apoptosis-inducing ligand-resistant thyroid cancer cells makes them susceptible to treatment with this ligand.Thyroid : official journal of the American Thyroid Association · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
MADD plays an essential role in cancer cell survival. Abrogation of endogenous MADD expression results in significant spontaneous apoptosis and enhanced susceptibility to tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, the regulation of MADD function is largely unknown. Here, we demonstrate that endogenous MADD is phosphorylated at three highly conserved sites by Akt, and only the phosphorylated MADD can directly interact with the TRAIL receptor DR4 thereby preventing Fas-associated death domain recruitment. However, in cells susceptible to TRAIL treatment, TRAIL induces a reduction in MADD phosphorylation levels resulting in MADD dissociation from, and Fas-associated death domain association with DR4, which allows death-inducing signaling complex (DISC) formation leading to apoptosis. Thus, the pro-survival function of MADD is dependent upon its phosphorylation by Akt. Because Akt is active in most cancer cells and phosphorylated MADD confers resistance to TRAIL-induced apoptosis, co-targeting Akt-MADD axis is likely to increase efficacy of TRAIL-based therapies.
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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.