J. Papkoff et al., WNT-1 REGULATES FREE POOLS OF CATENINS AND STABILIZES APC-CATENIN COMPLEXES, Molecular and cellular biology, 16(5), 1996, pp. 2128-2134
The Wnt-1 proto-oncogene induces the accumulation of beta-catenin and
plakoglobin, two related proteins that associate with and functionally
modulate the cadherin cell adhesion proteins, Here we have investigat
ed the effects of Wnt-1 expression on the tumor suppressor protein APC
, which also associates with catenins. Expression of Wnt-1 in two diff
erent cell lines greatly increased the stability of APC-catenin comple
xes. The steady-state levels of both catenins and APC were elevated by
Wnt-1, and the half-lives of both beta-catenin and plakoglobin associ
ated with APC were also markedly increased, The stabilization of caten
ins by Wnt-1 was primarily the result of a selective increase in the a
mount of uncomplexed, monomeric beta-catenin and plakoglobin, detected
both by affinity precipitation and size-exclusion chromatography of c
ell extracts, Exogenous expression of beta-catenin was possible in cel
ls already responding to Wnt-1 but not in the parental cells, suggesti
ng that Wnt-1 inhibits an essential regulatory mechanism for beta-cate
nin turnover, APC has the capacity to oppose this Wnt-1 effect in expe
riments in which overexpression of the central region of APC significa
ntly reduced the size of the monomeric pool of beta-catenin induced by
Wnt-1. Thus, the Wnt-1 signal transduction pathway leads to the accum
ulation of monomeric catenins and stabilization of catenin complex for
mation with both APC and cadherins.