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, 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.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Miyamoto Y,Futamura M,Kitamura N,Nakamura Y,Baba H,Arakawa Hdoi
10.3892/ijo_00000609subject
Has Abstractpub_date
2010-05-01 00:00:00pages
1253-60issue
5eissn
1019-6439issn
1791-2423journal_volume
36pub_type
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