Switching on-off Snail: LOXL2 versus GSK3beta.
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.
Peinado
Héctor
H
Departamento de Bioquímica, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomódicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Portillo
Francisco
F
Cano
Amparo
A
D000594:Amino Acid Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000594:Amino Acid Oxidoreductases; C485601:Loxl2 protein, mouse; D038362:Glycogen Synthase Kinase 3