Inhibition of Tcf3 binding by I-mfa domain proteins.
We have determined that I-mfa, an inhibitor of several basic helix-loop-helix (bHLH) proteins, and XIC, a Xenopus ortholog of human I-mf domain-containing protein that shares a highly conserved cysteine-rich C-terminal domain with I-mfa, inhibit the activity and DNA binding of the HMG box transcription factor XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embryos inhibited dorsal axis specification, the expression of the Tcf3/beta-catenin-regulated genes siamois and Xnr3, and the ability of beta-catenin to activate reporter constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate both the Wnt signaling pathway and a subset of bHLH proteins, possibly coordinating the activities of these two critical developmental pathways.
Snider
L
L
Fred Hutchinson Cancer Research Center, University of Washington Medical Center, Seattle, Washington 98109.
Thirlwell
H
H
Miller
J R
JR
Moon
R T
RT
Groudine
M
M
Tapscott
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017930:Genes, Reporter; D024002:HMGB Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495267:CTNNB1 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; C491077:Mdfi protein, mouse; D008869:Microtubule-Associated Proteins; D018006:Myogenic Regulatory Factors; C093133:SIA1 protein, Xenopus; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; C493963:Xicl protein, Xenopus; D051176:beta Catenin; C094620:nodal3.1 protein, Xenopus; D050760:Cyclin-Dependent Kinase Inhibitor p27