Functional Characterization of Snail2 Mediated E-Cadherin repression

Snail2, also called Slug, is a member of the Snail-family of zinc-finger transcription factors that plays a significant role both during development and carcinogenesis, by controlling epithelial-mesenchymal transition (EMT) processes. Snail2 has been also described as a direct transcriptional repression of E-cadherin during EMT being implicated as a prosurvival factor during tumorogenesis. Snail1 and Snail2 are highly homologous factors, containing a common N-terminal transrepressor domain (SNAG), a C-terminus DNA binding domain of four (Snail1) or five (Snail2) zinc fingers, and a divergent central region, which in Snail2 is formed by a unique domain called `Slug domain´ whose function remains to be elucidated. Snail1 repressor activity has been shown to be dependent on SNAG-mediated interaction with a repression complex formed by the corepressor mSin3a and histone deacetylases 1/2 (HDAC1/2). Importantly Snail1 transcription factor is further regulated through phosphorylation by various kinases. However, at date little is known about the control of Snail2 repressor activity. Here, we present interesting data shedding light into the regulation and function of Snail2 as a E-cadherin repressor. For this purpose we have performed ectopic expression of several Snail2 deletion mutants and examined the contribution of the specific domains to protein stability, localization and E-cadherin repressor activity. These data reveal a key role for the `Slug domain´ to repress E-cadherin expression. Furthermore, in vivo phosphorylation analysis revealed that specific phosphorylation on Snail2 protein is implicated in Snail2 function as a transcriptional repressor whose functional significance is currently being investigated