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Nuclear localization signals of the E-cadherin transcriptional repressor snail

Authors
 Hyeonseok Ko  ;  Hyun Sil Kim  ;  Jong In Yook  ;  Su Hyung Hong  ;  Kun Hong Kim  ;  Sang Hwy Lee  ;  Nam Hee Kim 
Citation
 CELLS TISSUES ORGANS, Vol.185(1-3) : 66-72, 2007 
Journal Title
CELLS TISSUES ORGANS
ISSN
 1422-6405 
Issue Date
2007
Abstract
The E-cadherin transcriptional repressor, Snail, plays a critical role in driving the epithelial-mesenchymal transition programs that mark gastrulation as well as invasion of cancer cells. Recent data suggest that Snail is phosphorylated by GSK3-β, resulting in β-TRCP-mediated ubiquitination and proteasomal degradation. Accordingly, Wnt signaling inhibits Snail phosphorylation, and consequently increases Snail protein levels. In the present study, we examine the function of nuclear localization motifs embedded within the Snail sequence. A typical bipartite nuclear localization signal (NLS) motif is located at the N-terminal of Snail, where it overlaps with the SNAG domain (residues 8–16), while a basic cluster NLS motif is found proximal to zinc finger domains (residues 151–152). Mutational inactivation of these NLS signals resulted in decreased levels of nuclear and total Snail protein as well as attenuated Snail repressor activity on an E-cadherin promoter construct, suggesting that NLS motifs are essential for proper function. In the presence of GSK3 inhibitor LiCl, the cytoplasmic levels of the NLS mutants increased, suggesting that cytosolic Snail undergoes rapid phosphorylation and degradation. Given the highly conserved nature of the Snail NLS motifs (from Xenopus to human), these results indicate that nuclear localization signals regulate Snail expression and subcellular localization via GSK3-β-dependent phosphorylation.
Full Text
http://www.karger.com/Article/FullText/101305
DOI
10.1159/000101305
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Lee, Sang Hwy(이상휘) ORCID logo https://orcid.org/0000-0002-9438-2489
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95819
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