Structure-based assessment and network analysis of targeting 14-3-3 proteins in prostate cancer
| Autor: | H. Alexander Ebhardt, Azadeh Beizaei, Alex Root |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Models Molecular Cancer Research Protein family YWHAZ Molecular Conformation Docetaxel Biology Proteomics urologic and male genital diseases Ligands lcsh:RC254-282 03 medical and health sciences Prostate cancer Structure-Activity Relationship 0302 clinical medicine 14-3-3 protein family LNCaP Drug Discovery Protein Interaction Mapping medicine Humans Protein Interaction Maps Letter to the Editor PI3K/AKT/mTOR pathway MM-GBSA Prostatic Neoplasms lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease BV02 3. Good health Androgen receptor 030104 developmental biology Oncology 14-3-3 Proteins Docking (molecular) 030220 oncology & carcinogenesis Multigene Family Cancer research Molecular Medicine Structure-based drug design Protein Binding |
| Zdroj: | Molecular Cancer Molecular Cancer, Vol 17, Iss 1, Pp 1-5 (2018) |
| ISSN: | 1476-4598 |
| Popis: | Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression. One such possible new target is YWHAZ of the 14-3-3 protein family as this gene has prognostic significance for metastatic CRPC patients. However, there are no small molecules targeting YWHAZ commercially available. Hence, we explored whether the small molecule BV02 targeting another 14-3-3 protein family member SFN also binds to YWHAZ. Using advanced docking algorithms we find that BV02 docks many other 14-3-3 family members. In addition, the amphipathic groove where drug binding occurs also has a high binding affinity for other drugs used to treat PCa such as docetaxel. The proteome of metastatic PCa models (LNCaP clone FGC and PC-3) was perturbed as a result of BV02 treatment. Through data integration of three proteomics data sets we found that BV02 modulates numerous protein-protein interactions involving 14-3-3 proteins in our PCa models. Electronic supplementary material The online version of this article (10.1186/s12943-018-0905-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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