Inhibition of Tcf3 binding by I-mfa domain proteins

Mol Cell Biol. 2001 Mar;21(5):1866-73. doi: 10.1128/MCB.21.5.1866-1873.2001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Blotting, Western
  • Cell Cycle Proteins*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Library
  • Genes, Reporter
  • HMGB Proteins*
  • Homeodomain Proteins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Myogenic Regulatory Factors / chemistry
  • Myogenic Regulatory Factors / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism
  • Tumor Suppressor Proteins*
  • Xenopus / embryology*
  • Xenopus Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, mouse
  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • HMGB Proteins
  • Homeodomain Proteins
  • Mdfi protein, mouse
  • Microtubule-Associated Proteins
  • Myogenic Regulatory Factors
  • SIA1 protein, Xenopus
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Tcf7l1 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Xenopus Proteins
  • Xicl protein, Xenopus
  • beta Catenin
  • nodal3.1 protein, Xenopus
  • Cyclin-Dependent Kinase Inhibitor p27