Zinc finger domain of Snail functions as a nuclear localization signal for importin β‐mediated nuclear import pathway

Abstract

Snail, a DNA-binding zinc finger protein, functions as a transcriptional repressor for genes including E-cadherin during development and the acquisition of tumor cell invasiveness. Human Snail is a 264-amino acid nuclear protein with an amino-terminal basic amino acid-rich domain (SNAG domain) and a carboxyl-terminal DNA-binding domain (zinc finger domain). A series of fusion proteins composed of green fluorescent protein (GFP) and portions of the Snail protein were generated, and their subcellular localization was examined. Fusion of the four zinc fingers to GFP led to the targeting of GFP to the nucleus, demonstrating that the zinc finger domain is sufficient for nuclear localization. Using an in vitro transport system, the nuclear import of Snail was reconstituted by importin (karyopherin) β β β β in the presence of Ran and NTF2. We further demonstrated that Snail binds directly to importin β β β β in a zinc finger domain-dependent manner. These results indicate that zinc finger domain of Snail functions as a nuclear localization signal and Snail can be transported into the nucleus in an importin β β β β -mediated manner.

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

“…Most of the RNF113-GFP signal colocalized with DAPI staining indicating nuclear localization, with a fraction having a granular cytosolic localization. This localization is consistent with the Zinc-Finger domain present in the RNF113 amino acid sequence (33). TNLA-GFP is localized to the plasma membrane and cytosol with about 10% of the signal colocalized with a fluorescent plasma membrane dye (Fig.…”

Snail, a transcriptional regulator, represses nephrin expression in glomerular epithelial cells of nephrotic rats

“…The zincfinger domain of Snail may function as the nuclear localization signal as reported. 39 In genes regulated by Snail, 40 there is great variation regarding the location of the E-box motifs. In accordance with the segment C1, Snail-mediated repression of claudin-7 is derived mainly from E-box motifs which are located downstream from the putative transcription start point.…”

Targeting the Nuclear Import Receptor Kpnβ1 as an Anticancer Therapeutic

“…17). Kpnb1 has been shown to be involved in the nuclear import of a number of EMT-promoting proteins, including Notch (18), Snail (19), and Smad (20). This role for Kpnb1 in promoting EMT suggests that it is necessary for cancer cell invasion and metastasis.…”