دورية أكاديمية
BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals
| العنوان: | BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals |
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| المؤلفون: | Srivastava, R, Cao, Z, Nedeva, C, Naim, S, Bachmann, D, Rabachini, T, Gangoda, L, Shahi, S, Glab, J, Menassa, J, Osellame, L, Nelson, T, Fernandez-Marrero, Y, Brown, F, Wei, A, Ke, F, O'Reilly, L, Doerflinger, M, Allison, C, Kueh, A, Ramsay, R, Smith, BJ, Mathivanan, S, Kaufmann, T, Puthalakath, H |
| بيانات النشر: | NATL ACAD SCIENCES |
| سنة النشر: | 2019 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | BCL-2 family proteins regulate the mitochondrial apoptotic pathway. BOK, a multidomain BCL-2 family protein, is generally believed to be an adaptor protein similar to BAK and BAX, regulating the mitochondrial permeability transition during apoptosis. Here we report that BOK is a positive regulator of a key enzyme involved in uridine biosynthesis; namely, uridine monophosphate synthetase (UMPS). Our data suggest that BOK expression enhances UMPS activity, cell proliferation, and chemosensitivity. Genetic deletion of Bok results in chemoresistance to 5-fluorouracil (5-FU) in different cell lines and in mice. Conversely, cancer cells and primary tissues that acquire resistance to 5-FU down-regulate BOK expression. Furthermore, we also provide evidence for a role for BOK in nucleotide metabolism and cell cycle regulation. Our results have implications in developing BOK as a biomarker for 5-FU resistance and have the potential for the development of BOK-mimetics for sensitizing 5-FU-resistant cancers. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0027-8424 1091-6490 |
| العلاقة: | pii: 1904523116; Srivastava, R., Cao, Z., Nedeva, C., Naim, S., Bachmann, D., Rabachini, T., Gangoda, L., Shahi, S., Glab, J., Menassa, J., Osellame, L., Nelson, T., Fernandez-Marrero, Y., Brown, F., Wei, A., Ke, F., O'Reilly, L., Doerflinger, M., Allison, C. ,. Puthalakath, H. (2019). BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 (31), pp.15469-15474. https://doi.org/10.1073/pnas.1904523116Test.; http://hdl.handle.net/11343/248414Test |
| الإتاحة: | https://doi.org/10.1073/pnas.1904523116Test http://hdl.handle.net/11343/248414Test |
| حقوق: | CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0Test |
| رقم الانضمام: | edsbas.472BD4E2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00278424 10916490 |
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