ArticleGenes & development2013
SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 destabilization.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- SRC-3/TRAF4 facilitates ovarian cancer development by activating the PI3K/AKT signaling pathway.Medical oncology (Northwood, London, England) · 2023Article
- AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer.Frontiers in endocrinology · 2023Review
- The Research Progress in Physiological and Pathological Functions of TRAF4.Frontiers in oncology · 2022Review
- Development of improved SRC-3 inhibitors as breast cancer therapeutic agents.Endocrine-related cancer · 2021Article
- SRC-3, a Steroid Receptor Coactivator: Implication in Cancer.International journal of molecular sciences · 2021Review
- Targeting NSD2-mediated SRC-3 liquid-liquid phase separation sensitizes bortezomib treatment in multiple myeloma.Nature communications · 2021Article
- USP7-Dependent Regulation of TRAF Activation and Signaling by a Viral Interferon Regulatory Factor Homologue.Journal of virology · 2020Article
- Roles of TRAFs in Ischemia-Reperfusion Injury.Frontiers in cell and developmental biology · 2020Review
- USP7: Structure, substrate specificity, and inhibition.DNA repair · 2019Review
- SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma.Cancer letters · 2019Article
- TRAF4-mediated ubiquitination of NGF receptor TrkA regulates prostate cancer metastasis.The Journal of clinical investigation · 2018Article
- USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells.Nature communications · 2018Article
- A novel isolation method for cancer prognostic factors via the p53 pathway by a combination ofOncoscience · 2018Article
- Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells.Scientific reports · 2018Article
- Genetic Alterations of TRAF Proteins in Human Cancers.Frontiers in immunology · 2018Review
- Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer.Journal of experimental & clinical cancer research : CR · 2017Article
- Cytoplasmic TRAF4 contributes to the activation of p70s6k signaling pathway in breast cancer.Oncotarget · 2015Article
- TRAF4 enhances oral squamous cell carcinoma cell growth, invasion and migration by Wnt-β-catenin signaling pathway.International journal of clinical and experimental pathology · 2015Article
- Impaired hematopoiesis and delayed thrombopoietic recovery following sublethal irradiation in SRC‑3 knockout mice.Molecular medicine reports · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Steroid receptor coactivator 3 (SRC-3) is an oncogenic nuclear receptor coactivator that plays a significant role in drug resistance. Using a lentiviral cDNA library rescue screening approach, we identified a SRC-3 downstream gene-TRAF4 (tumor necrosis factor [TNF] receptor associated-factor 4)-that functions in cell resistance to cytotoxic stress. TRAF4 expression is positively correlated with SRC-3 expression in human breast cancers. Similar to that observed for SRC-3 overexpression, breast cancer cells overexpressing TRAF4 are more resistant to stress-induced death. Here, we further dissected the underlying molecular mechanism for SRC-3 and TRAF4-mediated resistance to cytotoxic agents. We observed that SRC-3 expression is inversely correlated with the expression of p53-regulated proapoptotic genes in breast cancers and further found that SRC-3 and TRAF4 overexpression diminished cytotoxic stress-induced up-regulation of the tumor suppressor p53 protein. To determine the mechanism, we showed that the TRAF domain of TRAF4 bound to the N-terminal TRAF-like region of the deubiquitinase HAUSP (herpesvirus-associated ubiquitin-specific protease; also named USP7) and blocked the access of p53 to the same region of HAUSP. This TRAF4-mediated inhibition of HAUSP then led to the loss of p53 deubiquitination and its stabilization in response to cellular stress. Consistent with this cellular function, we also found that TRAF4 overexpression in breast cancer patients was associated significantly with poor prognosis. Because of SRC-3's ability to abrogate p53 function, our results suggest that SRC-3 overexpression may be especially important in tumors in which p53 is not mutated.
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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.