DEAD-box RNA helicase p68 is not required for nuclear translocation of β-catenin in colon cancer cells

Aberrant activation of the Wnt signal transduction pathway plays a pivotal role in the development of various human cancers, particularly those of the digestive tract. 1,2 A key component of this pathway is β-catenin, which drives the activation of specific target genes implicated in the control of cell proliferation and survival. In the absence of a Wnt signal, the activity of β-catenin is controlled by the cytoplasmic destruction complex. Within this complex, β-catenin is bound to the Axin and adenomatous polyposis coli (APC) proteins facilitating its phosphorylation by the protein kinases casein kinase 1α and glycogen synthase kinase 3β (GSK3p). Phosphorylated β-catenin is recognized by a specific E3 ubiquitin ligase complex containing the F-box protein β-TrCP, which mediates the ubiquitination and subsequent proteasomal degradation of β-catenin. In the presence of a Wnt signal, the cytoplasmic destruction complex dissociates preventing phosphorylation of β-catenin which leads to its stabilization. This enables β-catenin to enter the nucleus for interaction with members of the Tcf/Lef family of transcription factors ensuring efficient activation of specific target genes, such as c-myc and cyclin D1. 3 However, the molecular mechanism by which β-catenin translocates from the cytoplasm into the nucleus remains unclear, as previous studies suggested that the nuclear transport of β-catenin is independent of the classical nuclear localization signal/ importin machinery.4 Recently, Yang et al., reported that the tyrosine phosphorylated DEAD-box RNA helicase p68 promotes nuclear translocation of β-catenin in colon cancer cells by preventing GSK3β mediated phosphorylation and displacing Axin from β-catenin. 5 This intriguing finding may provide further insight into the mechanism controlling nuclear translocation of β-catenin and subsequent gene expression.