| First Author | Miyamoto Y | Year | 2010 |
| Journal | Int J Oncol | Volume | 36 |
| Issue | 5 | Pages | 1253-60 |
| PubMed ID | 20372800 | Mgi Jnum | J:172540 |
| Mgi Id | MGI:5008229 | Doi | 10.3892/ijo_00000609 |
| Citation | Miyamoto Y, et al. (2010) Identification of UNC5A as a novel transcriptional target of tumor suppressor p53 and a regulator of apoptosis. Int J Oncol 36(5):1253-60 |
| abstractText | UNC5A is an axon-guidance molecule, and plays a critical role in neuronal development and differentiation as a netrin-1 receptor. Emerging evidence suggests that axon guidance molecules including UNC5A regulate apoptosis in non-neuronal cells. Here, we report that UNC5A regulates apoptosis as a downstream target of p53. UNC5A expression was strongly induced by exogenous and endogenous p53. Chromatin immunoprecipitation (ChIP) revealed that p53 binds to a sequence in the promoter region of the UNC5A gene. Reporter assays showed that this sequence exhibits p53-dependent transcriptional activity. Overexpression of UNC5A significantly suppressed colony formation of two glioblastoma cell lines-U373MG and T98G. UNC5A dramatically induced apoptosis through the activation of caspase-3 in various cancer cell lines, including LS174T (colon cancer), U373MG (glioblastoma), SH-SY5Y (neuroblastoma), and SKNAS (neuroblastoma). Finally, gamma irradiation strongly induced the expression of UNC5A mRNA in the spleen and colon of p53+/+ mice, but not in those of p53-/- mice, implying that the transcription of UNC5A in vivo is regulated by p53. These results suggest that UNC5A is a novel transcriptional target of p53 and plays a role in p53-dependent apoptosis. |
