دورية أكاديمية
Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells
| العنوان: | Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells |
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| المؤلفون: | Gajula, Rajendra P., Chettiar, Sivarajan T., Williams, Russell D., Nugent, Katriana, Kato, Yoshinori, Wang, Hailun, Malek, Reem, Taparra, Kekoa, Cades, Jessica, Annadanam, Anvesh, Yoon, A.-Rum, Fertig, Elana, Firulli, Beth A., Mazzacurati, Lucia, Burns, Timothy F., Firulli, Anthony B., An, Steven S., Tran, Phuoc T. |
| المساهمون: | Department of Pediatrics, IU School of Medicine |
| المصدر: | Publisher |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2015 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Basic Helix-Loop-Helix Transcription Factors, metabolism, Nuclear Proteins, Prostatic Neoplasms, Protein Interaction Domains and Motifs, Twist Transcription Factor |
| الوصف: | The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1476-5586 |
| العلاقة: | Neoplasia (New York, N.Y.); Gajula, R. P., Chettiar, S. T., Williams, R. D., Nugent, K., Kato, Y., Wang, H., … Tran, P. T. (2015). Structure-Function Studies of the bHLH Phosphorylation Domain of TWIST1 in Prostate Cancer Cells. Neoplasia (New York, N.Y.), 17(1), 16–31. http://doi.org/10.1016/j.neo.2014.10.009Test; https://hdl.handle.net/1805/9244Test |
| الإتاحة: | https://doi.org/10.1016/j.neo.2014.10.009Test https://hdl.handle.net/1805/9244Test |
| حقوق: | Attribution-NonCommercial-NoDerivs 3.0 Unported ; http://creativecommons.org/licenses/by-nc-nd/3.0/usTest |
| رقم الانضمام: | edsbas.25FC761 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14765586 |
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