title: Akt2 interacts with Snail1 in the E-cadherin promoter.
abstract: Snail1 is a transcriptional factor essential for triggering epithelial-to-mesenchymal transition. Moreover, Snail1 promotes resistance to apoptosis, an effect associated to PTEN gene repression and Akt stimulation. In this article we demonstrate that Snail1 activates Akt at an additional level, as it directly binds to and activates this protein kinase. The interaction is observed in the nucleus and increases the intrinsic Akt activity. We determined that Akt2 is the isoform interacting with Snail1, an association that requires the pleckstrin homology domain in Akt2 and the C-terminal half in Snail1. Snail1 enhances the binding of Akt2 to the E-cadherin (CDH1) promoter and Akt2 interference prevents Snail1 repression of CDH1 gene. We also show that Snail1 binding increases Akt2 intrinsic activity on histone H3 and have identified Thr45 as a residue modified on this protein. Phosphorylation of Thr45 in histone H3 is sensitive to Snail1 and Akt2 cellular levels; moreover, Snail1 upregulates the binding of phosphoThr45 histone H3 to the CDH1 promoter. These results uncover an unexpected role of Akt2 in transcriptional control and point out to phosphorylation of Thr45 in histone H3 as a new epigenetic mark related to Snail1 and Akt2 action.
authors.affiliation: Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Villagrasa
authors.forename: V M
authors.initials: VM
authors.lastname: Díaz
authors.forename: R
authors.initials: R
authors.lastname: Viñas-Castells
authors.forename: S
authors.initials: S
authors.lastname: Peiró
authors.forename: B
authors.initials: B
authors.lastname: Del Valle-Pérez
authors.forename: N
authors.initials: N
authors.lastname: Dave
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Asiain
authors.forename: J I
authors.initials: JI
authors.lastname: Casal
authors.forename: J M
authors.initials: JM
authors.lastname: Lizcano
authors.forename: M
authors.initials: M
authors.lastname: Duñach
authors.forename: A
authors.initials: A
authors.lastname: García de Herreros
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C067625:FN1 protein, human; D005353:Fibronectins; D006657:Histones; D007527:Isoenzymes; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt