The Wnt/beta-catenin pathway is a conserved cell-cell signalling mechanism in animals that regulates gene expression via TCF/LEF DNA-binding factors to coordinate many cellular processes. Vertebrates normally have four Tcf/Lef genes, which, through alternative splicing and alternative promoter use give rise to a variety of TCF/LEF isoforms. Recent evidence from several experimental systems sugg...

T-cell factor/lymphoid enhancer factor (TCF/LEF) proteins regulate transcription by recruiting β-catenin and its associated co-regulators. Whether TCF/LEFs also recruit more factors through independent, direct interactions is not well understood. Here we discover Ring Finger Protein 14 (RNF14) as a new binding partner for all TCF/LEF transcription factors. We show that RNF14 positively regulate...

Secreted proteins of the Wnt family have profound organizing roles during animal development and are transduced via the activities of the Frizzled (Fz) class of transmembrane receptors and the TCF/LEF/Pangolin class of transcription factors. beta-catenins, including Drosophila Armadillo (Arm), link activation of Fz at the cell surface to transcriptional regulation by TCF in the nucleus. The con...

Lymphoid-enhancing factor/T-cell factors (LEF1/TCF) are a high-mobility group of transcriptional factors that play essential roles in cell fate determination during early embryogenesis and ontogenesis. Aberrant activations of LEF1/TCF-mediated transcription have been implicated in a variety of malignancies. Our recent studies on vertebrate embryogenesis identified Xom, a homeobox protein of the...

Members of the Tcf/Lef family of the HMG box transcription factors are nuclear effectors of the Wnt signal transduction pathway. Upon Wnt signaling, TCF/LEF proteins interact with beta-catenin and activate transcription of target genes, while, in the absence of the Wnt signal, TCFs function as transcriptional repressors. All vertebrate Tcf/Lef transcription factors associate with TLE/Groucho-re...

T cell factor 1 (TCF-1) is a transcription factor known to act downstream of the canonical Wnt pathway and is essential for normal T cell development. However, its physiological roles in mature CD8(+) T cell responses are unknown. Here we showed that TCF-1 deficiency limited proliferation of CD8(+) effector T cells and impaired their differentiation toward a central memory phenotype. Moreover, ...

About 15% of sporadic colorectal cancers show microsatellite instability (MSI) due to the inactivation of mismatch repair genes and are termed MSI-H tumors. In these tumors, frameshift mutations in coding repeats have been found within the TGFbeta-RII, BAX, and IGFRII genes that are probably involved in their progression. In the present work, we report frequent mutations in TCF-4, another targe...

OBJECTIVE To elucidate the cellular function of Kaposi's sarcoma-associated herpesvirus (KSHV) replication transactivation activator (RTA) at the transcriptional level. METHODS Transcriptional activation of T-cell-factor (TCF)-dependent genes by RTA was determined using the luciferase reporter assay. The specific regions of RTA required for the activation of TCF-dependent transcription and as...

MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, m...