PMID- 10080941
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 256
IP  - 3
DP  - 1999 Mar 24
TI  - Identification of Tcf4 residues involved in high-affinity beta-catenin binding.
PG  - 584-90
AB  - The N-termini of members of the T-cell factor (Tcf) and lymphocyte-enhancement
      factor (Lef) protein families bind to beta-catenin, forming bipartite
      transcription factors which regulate expression of genes involved in organismal
      development and the growth of normal and malignant colon epithelium. Elevated
      levels of Tcf4:beta-catenin are found in colon tumor cells with mutations in the 
      adenomatous polyposis coli (APC) gene. The elevated levels of Tcf4:beta-catenin
      result in increased transcription of genes, including c-myc, important for the
      growth of these tumor cells. Here we analyze the interaction between beta-catenin
      and Tcf4 and show that the N-terminal 53 amino acids of Tcf4 bind with high
      affinity to beta-catenin. We show that this high-affinity interaction involves
      multiple contact points including Tcf4 Asp-16, which is essential for
      beta-catenin binding. In addition to Tcf/Lef family members, beta-catenin binds
      to APC and cadherins. We found that the binding of beta-catenin to Tcf4, APC, or 
      E-cadherin was mutually exclusive. These results are discussed with regard to how
      beta-catenin interacts with its binding partners and to the potential for
      identifying specific, small molecule inhibitors of these interactions.
CI  - Copyright 1999 Academic Press.
FAU - Omer, C A
AU  - Omer CA
AD  - Department of Cancer Research, Merck Research Laboratories, Sumneytown Pike, West
      Point, Pennsylvania, 19486, USA. chuck_omer@merck.com
FAU - Miller, P J
AU  - Miller PJ
FAU - Diehl, R E
AU  - Diehl RE
FAU - Kral, A M
AU  - Kral AM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Amino Acids)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Amino Acids/analysis/genetics/*metabolism
MH  - Aspartic Acid/genetics/metabolism
MH  - Binding, Competitive
MH  - Cadherins/chemistry/genetics/metabolism
MH  - Conserved Sequence
MH  - Cytoskeletal Proteins/chemistry/genetics/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Leucine/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Sequence Deletion
MH  - Solubility
MH  - TCF Transcription Factors
MH  - *Trans-Activators
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - beta Catenin
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - S0006-291X(99)90379-0 [pii]
AID - 10.1006/bbrc.1999.0379 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Mar 24;256(3):584-90. doi:
      10.1006/bbrc.1999.0379.