Schematic diagram of ZO-2 as a scaffold for transcription and splicing. ZO-2 expression blocks GSK-3β inhibitory phosphorylation at Ser9. GSK-3β phosphorylates β-catenin and targets it for ubiquitination and proteasomal degradation. Consequently, β-catenin entry into the nucleus and transcriptional activity is inhibited. At the nucleus, ZO-2 localizes in speckles associated to PIP2 and ZASP and inhibits transcription of CD1 through its interaction with an E-box in the promoter region, mediated by c-Myc transcription factor. In addition, ZO-2 is proposed to participate in mRNA splicing due to its association with the essential splicing protein SC-35 and the scaffold attachment factor SAF-B. S/MAR, scaffold/matrix attachment región; P, phosphate; Ub, ubiquitin; U2, U5, and U6, splicing ribonucleoproteins; PIP2, phosphatidylinositol (4,5)-bisphosphate.