P-Catenin has essential roles in morphogenesis and human cancer, both as a subunit of adhesive complexes in the cell membrane and as a transcriptional coactivator in the Writ signaling pathway. In addition, beta-catenin also has the ability to transport lymphoid enhancer binding factor-1 into the nucleus. In this study, we examined a constitutive active mutation, beta-catenin (T41A, S45A), for its potential as a nuclear import receptor for T-cell transcription factor 4 in 293 cells. Immunoblot analysis demonstrated that this constitutive active form of beta-catenin increased the amount of Tcf4 in the nucleus about 4-5-fold compared to controls. However, the overall expression of Tcf4 remained the same with or without over-expression of beta-catenin (T41A, S45A). T-cell transcription factor 4 reporter gene and electrophoretic mobility shift assay further indicated that the increase in Tcf4 in the nucleus was consistent with its accrued DNA binding capacity and transcription activity. Microscopic immunofluorescence examination showed that Tcf4 was mainly located in the cytoplasm and transported into the nucleus, without or with over-expression of beta-catenin (T41A, S45A), respectively. Our results suggest that beta-catenin might be a major factor regulating the import of Tcf4 from the cytoplasm into the nucleus, consequently controlling its transcription activity. (c) 2006 Elsevier Inc. All rights reserved.