| First Author | Srivastava R | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 31 | Pages | 15469-15474 |
| PubMed ID | 31311867 | Mgi Jnum | J:278333 |
| Mgi Id | MGI:6342658 | Doi | 10.1073/pnas.1904523116 |
| Citation | Srivastava R, et al. (2019) BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals. Proc Natl Acad Sci U S A 116(31):15469-15474 |
| abstractText | 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. |
