DELETION OF AN AMINO-TERMINAL SEQUENCE STABILIZES BETA-CATENIN IN-VIVO AND PROMOTES HYPERPHOSPHORYLATION OF THE ADENOMATOUS POLYPOSIS-COLI TUMOR-SUPPRESSOR PROTEIN
S. Munemitsu et al., DELETION OF AN AMINO-TERMINAL SEQUENCE STABILIZES BETA-CATENIN IN-VIVO AND PROMOTES HYPERPHOSPHORYLATION OF THE ADENOMATOUS POLYPOSIS-COLI TUMOR-SUPPRESSOR PROTEIN, Molecular and cellular biology, 16(8), 1996, pp. 4088-4094
Regulation of cell adhesion and cell signaling by beta-catenin occurs
through a mechanism likely involving the targeted degradation of the p
rotein. Deletional analysis was used to generate a beta-catenin refrac
tory to rapid turnover and to examine its effects on complexes contain
ing either cadherin or the adenomatous polyposis coli (APC) protein. T
he results show that amino-terminal deletion of beta-catenin results i
n a protein with increased stability that acts in a dominant fashion w
ith respect to wild-type beta-catenin. Constitutive expression in AtT2
0 cells of a beta-catenin lacking 89 N-terminal amino acids (Delta N89
beta-catenin) resulted in severely reduced levels of the more labile
wild-type beta-catenin. The mutant beta-catenin was expressed at endog
enous levels but displaced the vast majority of wild-type beta-catenin
associated with N-cadherin. The Delta N89 beta-catenin accumulated on
the APC protein to a level 10-fold over that of wild-type beta-cateni
n and recruited a kinase into the APC complex. The kinase was highly a
ctive toward APC in vitro and promoted a sodium dodecyl sulfate gel ba
nd shift that was also evident for endogenous APC from cells expressin
g the mutant beta-catenin. Unlike wild-type beta-catenin, which partit
ions solely as part of a high-molecular-weight complex, the Delta N89
mutant protein also fractionated as a stable monomer, indicating that
it had escaped the requirement to associate with other proteins. That
similar N-terminal mutants of beta-catenin have been implicated in cel
lular transformation suggests that their abnormal association with APC
may, in part, be responsible for this phenotype.