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Cell Cycle. 2005 Dec;4(12):1749-52. Epub 2005 Dec 5.

Switching on-off Snail: LOXL2 versus GSK3beta.

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  • 1Departamento de Bioquímica, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomódicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.


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.

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