TCF transcription factors: molecular switches in carcinogenesis.
Although originally cloned as lymphoid transcription factors, members of the T-cell factor (Tcf) family are now well recognized as key activators/repressors in many developmental processes. Transcriptionally inert Tcf factors become potent transactivators upon interaction with the Wnt signaling product beta-catenin or its Drosophila counterpart Armadillo. In contrast, Tcf proteins mediate repression when bound to members of the Groucho family of transcriptional repressors, CBP and CtBP. Recently, Tcf factors have been reported as tumor inducers, aberrantly activating their target genes as a result of elevated beta-catenin levels in many types of cancer. These abnormal beta-catenin levels are usually caused by stabilizing mutations in beta-catenin itself or truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. In this review, we will give a chronological overview of the Tcf factors and the phenotypes of Tcf mutant mice, as well as Tcf-binding partners. We will discuss Tcf signaling upon interaction with different partners, resulting in activator and repressor roles of Tcf factors in the light of carcinogenic events.
Roose
J
J
Department of Immunology, Center for Biomedical Genetics, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.
Clevers
H
H
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C496491:hnf1a protein, zebrafish; C074622:wg protein, Drosophila; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta