Chen J Y, Yang L X, Huang Z F
Sun Yat-sen University, Zhongshan School of Medicine, Institute of Human Virology, Guangzhou, China.
Braz J Med Biol Res. 2013 Dec;46(12):1021-1027. doi: 10.1590/1414-431X20132833. Epub 2013 Dec 2.
Siva-1 induces apoptosis in multiple pathological processes and plays an important role in the suppression of tumor metastasis, protein degradation, and other functions. Although many studies have demonstrated that Siva-1 functions in the cytoplasm, a few have found that Siva-1 can relocate to the nucleus. In this study, we found that the first 33 amino acid residues of Siva-1 are required for its nuclear localization. Further study demonstrated that the green fluorescent protein can be imported into the nucleus after fusion with these 33 amino acid residues. Other Siva-1 regions and domains showed less effect on Siva-1 nuclear localization. By site-mutagenesis of all of these 33 amino acid residues, we found that mutants of the first 1-18 amino acids affected Siva-1 nuclear compartmentalization but could not complete this localization independently. In summary, we demonstrated that the N-terminal 33 amino acid residues were sufficient for Siva-1 nuclear localization, but the mechanism of this translocation needs additional investigation.
Siva-1在多种病理过程中诱导细胞凋亡,并在抑制肿瘤转移、蛋白质降解及其他功能中发挥重要作用。尽管许多研究表明Siva-1在细胞质中发挥作用,但也有一些研究发现Siva-1可重新定位于细胞核。在本研究中,我们发现Siva-1的前33个氨基酸残基是其核定位所必需的。进一步研究表明,绿色荧光蛋白与这33个氨基酸残基融合后可被导入细胞核。Siva-1的其他区域和结构域对Siva-1的核定位影响较小。通过对这33个氨基酸残基进行全位点诱变,我们发现前1-18个氨基酸的突变体影响Siva-1的核分隔,但不能独立完成这种定位。总之,我们证明了N端33个氨基酸残基足以实现Siva-1的核定位,但其转运机制仍需进一步研究。