Identification of UNC5A as a novel transcriptional target of tumor suppressor p53 and a regulator of apoptosis

  • Authors: Yuji Miyamoto, Manabu Futamura, Noriaki Kitamura, Yasuyuki Nakamura, Hideo Baba, Hiroufmi Arakawa
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  • Published online on: Saturday, May 1, 2010
  • Pages: 1253-1260
  • DOI: 10.3892/ijo_00000609

Abstract

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, γ 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.
Journal Cover

May 2010
Volume 36 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Miyamoto, Y., Futamura, M., Kitamura, N., Nakamura, Y., Baba, H., & Arakawa, H. (2010). Identification of UNC5A as a novel transcriptional target of tumor suppressor p53 and a regulator of apoptosis. International Journal of Oncology, 36(5), 1253-1260.
MLA
Miyamoto, Futamura, Kitamura, Nakamura, Baba, and Hiroufmi Arakawa. "Identification of UNC5A as a novel transcriptional target of tumor suppressor p53 and a regulator of apoptosis." International Journal of Oncology International Journal of Oncology 36.5 (2010): 1253-1260.
Chicago
Miyamoto, Futamura, Kitamura, Nakamura, Baba, and Hiroufmi Arakawa. "Identification of UNC5A as a novel transcriptional target of tumor suppressor p53 and a regulator of apoptosis." International Journal of Oncology International Journal of Oncology 36 no. 5 (2010): 1253-1260.