TCF/LEF Transcription Factors: An Update from the Internet Resources.

Dusan Hrckulak,Vladimir Korinek,Michal Kolar,Hynek Strnad

doi:10.3390/cancers8070070

Abstract

T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins (TCFs) from the High Mobility Group (HMG) box family act as the main downstream effectors of the Wnt signaling pathway. The mammalian TCF/LEF family comprises four nuclear factors designated TCF7, LEF1, TCF7L1, and TCF7L2 (also known as TCF1, LEF1, TCF3, and TCF4, respectively). The proteins display common structural features and are often expressed in overlapping patterns implying their redundancy. Such redundancy was indeed observed in gene targeting studies; however, individual family members also exhibit unique features that are not recapitulated by the related proteins. In the present viewpoint, we summarized our current knowledge about the specific features of individual TCFs, namely structural-functional studies, posttranslational modifications, interacting partners, and phenotypes obtained upon gene targeting in the mouse. In addition, we employed several publicly available databases and web tools to evaluate the expression patterns and production of gene-specific isoforms of the TCF/LEF family members in human cells and tissues.

Highlights

The Wnt signaling pathway is one of the major signaling mechanisms regulating cell-fate decisions during embryogenesis and in adult tissues
N-terminus by the β-catenin destruction complex composed of two scaffolding proteins, adenomatous polyposis coli (APC) and axis inhibition protein (Axin), and two serine/threonine kinases, casein kinase 1 alpha (CK1α) and glycogen synthase kinase 3 (GSK3)
The C-terminal binding proteins were described as short-range transcriptional corepressors; the results obtained in Drosophila documented that CtBP might act as both activator and repressor of Wnt target genes in a context-dependent manner

Summary

Introduction

The Wnt signaling pathway is one of the major signaling mechanisms regulating cell-fate decisions during embryogenesis and in adult tissues. Nuclear DNA-binding TCF/LEF proteins and their transcriptional cofactor β-catenin represent the key components of the canonical branch of the pathway. 5/6 leads to the recruitment of Axin to the membrane and functional inactivation of the β-catenin destruction complex. This results in cytoplasmic and nuclear β-catenin accumulation. Β-catenin associates with TCFs to activate transcription of Wnt signaling target genes [1,2,3]. LEF1 is perceived as the the the unique functions of individual TCFs. From the historical perspective, LEF1 is perceived as main transcriptional transcriptional activator, activator, and and TCF7L1—despite. TCFs produced in multiple isoforms generated on TCFs areare produced in multiple isoforms generated by by mRNA splicing or alternative promoter usage. Target gene activation or selection (reviewed in [11])

Structural

Functional Properties and Isoform Expression of Individual TCFs

TCF7L1

Findings

TCF7L2