Switching on-off Snail: LOXL2 versus GSK3beta

Cell Cycle. 2005 Dec;4(12):1749-52. doi: 10.4161/cc.4.12.2224. Epub 2005 Dec 5.

Abstract

Epithelial-mesenchymal transition (EMT) is considered as an essential determinant of carcinoma progression. The transcription factor Snail controls EMT by repressing E-cadherin gene expression and other epithelial genes. Snail protein stability and cellular localization is finely controlled by GSK3beta-dependent phosphorylation and subsequent ubiquitination. GSK3beta phosphorylates Snail at two different motifs which induce its nuclear export and association with beta-Trcp thus leading to Snail degradation. Recently, Snail was found to interact physical and functionally with LOXL2, a member of the lysyl oxidase gene family. Interestingly, LOXL2 seems to attenuate the GSK3beta-dependent Snail degradation. Here, we discuss the relevance of this new potential mechanism of regulation and the role of LOXL2 during carcinoma progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / chemistry
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Neoplasms / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism*

Substances

  • Snail Family Transcription Factors
  • Transcription Factors
  • Amino Acid Oxidoreductases
  • Loxl2 protein, mouse
  • Glycogen Synthase Kinase 3