The N-terminal 33 amino acid domain of Siva-1 is sufficient for nuclear localization

Abstract

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 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway

“…Siva-1 was elucidated by Prasad et al (8) from a Hela cell library using yeast two-hybrid screening with a tumor necrosis factor receptor. although numerous studies (9)(10)(11) have demonstrated that Siva-1 functions in the cytoplasm, studies have also determined that Siva-1 can relocate into the nucleus (12,13). The human Siva…”

Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

“… 5 Siva-1 is also capable of entering the nucleus, for which the first 33 N-terminal amino acids are required (probably amino acids 1–18 are the most important). 6 Siva-1 is typically transcribed through the p53 tumor suppressor, similarly as other apoptotic genes. This occurs typically during the neuronal cell death in neurodegeneration or injury.…”