Mouse Uaca (or nucling) is thought to interact with the Apaf1/pro-caspase-9 complex, thereby acting as a stabilizer for the apoptosome (Sakai T et al. 2004). Uaca was shown to induce apoptosis in mammalian cells (Sakai T et al. 2004). Cells prepared from Uaca-knockout mice were resistant to proapoptotic stress induced by UV irradiation, LPS ot TNFalpha (Sakai T et al. 2004; Kim SM et al. 2013). Moreover, Uaca-deficiency in mice was linked to the development of hepatic inflammation and hepatocellular carcinoma (HCC) (Sakai T et al. 2010). The findings in mouse disease model are in line with the data showing a significantly lower expression of UACA mRNAs and protein levels in human non-small cell lung carcinoma (NSCLC) cell lines and NSCLC tumours suggesting that the loss of UACA might contribute to tumor progression due to a reduction in the UACA-assistedcell death (Moravcikova E et al. 2012).
The mechanism of the UACA proapoptotic activity remains unclear. Mouse Uaca, showing both cytoplasmic and perinuclear/nuclear localization, was suggested to translocate Apaf1-apoptosome to the nucleus after proapoptotic stress (Sakai T et al. 2004). Uaca also reduced expression of the NFkappaB-targeted genes by preventing the nuclear translocation of NFkappaB (Liu L et al. 2004).
Shishido, Y, Ishimura, K, Mak, TW, Toida, K, Kaji, R, Shimada, H, Sakai, T, Mitani, T, Fukui, K, Teng, X, Mukai-Sakai, R, Matsumoto, M, Liu, L
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