AI Article Synopsis
- Oncoproteins and tumor suppressors interact in opposing ways to control cancer growth and spread.
- Researchers found that phosphorylation of ETS1 and ETS2 oncoproteins creates sites for the COP1 tumor suppressor to target them for destruction.
- In breast cancer cells, the phosphorylation of a nearby tyrosine residue on ETS1 prevents COP1 from binding, allowing ETS1 to accumulate and promote unchecked tumor growth.
Article Abstract
Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169234 | PMC |
| http://dx.doi.org/10.1016/j.ccr.2014.06.026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrating machine learning and structure-based approaches for repurposing potent tyrosine protein kinase Src inhibitors to treat inflammatory disorders.
Sci Rep
January 2025
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
Tyrosine-protein kinase Src plays a key role in cell proliferation and growth under favorable conditions, but its overexpression and genetic mutations can lead to the progression of various inflammatory diseases. Due to the specificity and selectivity problems of previously discovered inhibitors like dasatinib and bosutinib, we employed an integrated machine learning and structure-based drug repurposing strategy to find novel, targeted, and non-toxic Src kinase inhibitors. Different machine learning models including random forest (RF), k-nearest neighbors (K-NN), decision tree, and support vector machine (SVM), were trained using already available bioactivity data of Src kinase targeting compounds.
View Article and Find Full Text PDF[Effects of Xihuang Pills on angiogenesis, invasion, and metastasis of p rostate cancer based on FAK/Src/ERK pathway].
Zhongguo Zhong Yao Za Zhi
December 2024
Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prescription and Transformation, Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Tumor Prevention Mechanism of Traditional Chinese Medicine,Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Traditional Chinese Medicine Tumour in Hunan Universities, Hunan University of Chinese Medicine Changsha 410208, China College of Integrative Medicine, Hunan University of Chinese Medicine Changsha 410208, China.
Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills.
View Article and Find Full Text PDFSRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.
Commun Biol
January 2025
Institute of Urology, The Second Hospital of Lanzhou University, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu, China.
The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance.
View Article and Find Full Text PDFPrevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.
Theranostics
January 2025
College of Pharmacy, Research Institute of Pharmaceutical Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea.
Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% of all solid tumor patients. However, its non-specific, cell-killing property leads to inevitable damage to surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue damage contributes to the formation of a pro-tumorigenic microenvironment.
View Article and Find Full Text PDFSingle-Cell RNA Sequencing, Cell Communication, and Network Pharmacology Reveal the Potential Mechanism of Buch.-Ham in Hepatocellular Carcinoma Inhibition.
Pharmaceuticals (Basel)
December 2024
School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Background: Hepatocellular carcinoma (HCC), a prevalent form of primary liver malignancy, arises from liver-specific hepatocytes. Buch.-Ham(Climbing senecio) is a bitter-tasting plant of the Compositae family with anti-tumor properties.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!