TY - JOUR
T1 - The deubiquitinating enzyme Fam interacts with and stabilizes β-catenin
AU - Taya, Shinichiro
AU - Yamamoto, Takaharu
AU - Kanai-Azuma, Masami
AU - Wood, Stephen A.
AU - Kaibuchi, Kozo
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Background: In the ubiquitin-proteasome pathway, the ubiquitinated substrates either undergo degradation by the proteasome or stabilization through the action of the deubiquitinating enzyme. We have previously found that the deubiquitinating enzyme Fam is colocalized with AF-6, one of the effectors of the Ras small GTPase, at cell-cell contact sites in epithelial cells and interacts with AF-6 in vivo and in vitro. Fam has deubiquitinating activity in vitro and prevents the ubiquitination of AF-6 in intact cells. The degradation of β-catenin, which accumulates at the cell-cell contact sites as a cadherin/catenin complex, is thought to be regulated by the ubiquitin-proteasome pathway. These observations prompted us to examine the possible Fam regulation of the stabilization of β-catenin. Results: We found that Fam interacted with β-catenin both in vivo and in vitro. The Fam- binding site of β-catenin mapped to the region close to the APC or Axin- binding site of β-catenin. Overexpression of Fam in mouse L cells resulted in an elevation of β-catenin levels and in an elongation of the half-life of β-catenin. In these L cells, Fam was colocalized with β-catenin at the dot- like structures in the cytoplasm. Conclusion: These results indicate that Fam interacts with and stabilizes β-catenin in vivo, presumably through the deubiquitination of β-catenin.
AB - Background: In the ubiquitin-proteasome pathway, the ubiquitinated substrates either undergo degradation by the proteasome or stabilization through the action of the deubiquitinating enzyme. We have previously found that the deubiquitinating enzyme Fam is colocalized with AF-6, one of the effectors of the Ras small GTPase, at cell-cell contact sites in epithelial cells and interacts with AF-6 in vivo and in vitro. Fam has deubiquitinating activity in vitro and prevents the ubiquitination of AF-6 in intact cells. The degradation of β-catenin, which accumulates at the cell-cell contact sites as a cadherin/catenin complex, is thought to be regulated by the ubiquitin-proteasome pathway. These observations prompted us to examine the possible Fam regulation of the stabilization of β-catenin. Results: We found that Fam interacted with β-catenin both in vivo and in vitro. The Fam- binding site of β-catenin mapped to the region close to the APC or Axin- binding site of β-catenin. Overexpression of Fam in mouse L cells resulted in an elevation of β-catenin levels and in an elongation of the half-life of β-catenin. In these L cells, Fam was colocalized with β-catenin at the dot- like structures in the cytoplasm. Conclusion: These results indicate that Fam interacts with and stabilizes β-catenin in vivo, presumably through the deubiquitination of β-catenin.
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U2 - 10.1046/j.1365-2443.1999.00297.x
DO - 10.1046/j.1365-2443.1999.00297.x
M3 - Article
C2 - 10620020
AN - SCOPUS:0033392501
SN - 1356-9597
VL - 4
SP - 757
EP - 767
JO - Genes to Cells
JF - Genes to Cells
IS - 12
ER -