PMID- 10318824
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 20
DP  - 1999 May 14
TI  - Functional domains of axin. Importance of the C terminus as an oligomerization
      domain.
PG  - 14090-3
AB  - To understand the mechanism of how Axin acts as an inhibitory molecule in the Wnt
      pathway, we generated a series of mutated forms of Axin. From the binding
      experiments, we defined the domains of Axin that bind glycogen synthase
      kinase-3beta (GSK-3beta) and beta-catenin. We also examined the ability of each
      Axin mutant to inhibit lymphoid enhancer factor-1 (Lef-1) reporter activity in a 
      cell line expressing high levels of beta-catenin. Axin mutants that did not bind 
      GSK-3beta or beta-catenin were ineffective in suppressing Lef-1 reporter
      activity. Binding GSK-3beta and beta-catenin was not sufficient for this
      inhibitory effect of Axin. Axin mutants with C-terminal truncations lacked the
      ability to inhibit Lef-1 reporter activity, even though they bound GSK-3beta and 
      beta-catenin. The C-terminal region was required for binding to Axin itself.
      Substitution of the C-terminal region with an unrelated dimerizing molecule, the 
      retinoid X receptor restored its inhibitory effect on Lef-1-dependent
      transcription. The oligomerization of Axin through its C terminus is important
      for its function in regulation of beta-catenin-mediated response.
FAU - Sakanaka, C
AU  - Sakanaka C
AD  - Cardiovascular Research Institute, University of California, San Francisco,
      California 94143-0130, USA.
FAU - Williams, L T
AU  - Williams LT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (LEF1 protein, human)
RN  - 0 (Lef1 protein, mouse)
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Axin Protein
MH  - Binding Sites
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Colonic Neoplasms/genetics/metabolism
MH  - Cytoskeletal Proteins/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Humans
MH  - Lymphoid Enhancer-Binding Factor 1
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Protein Conformation
MH  - Proteins/chemistry/genetics/*physiology
MH  - *Repressor Proteins
MH  - Structure-Activity Relationship
MH  - *Trans-Activators
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
MH  - beta Catenin
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1074/jbc.274.20.14090 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):14090-3. doi: 10.1074/jbc.274.20.14090.