Abstract
CBP and its homologue p300 play significant roles in cell differentiation, cell cycle, and anti-oncogenesis. We demonstrated that beta-catenin, recently known as a potent oncogene, and CBP/p300 are associated through its CH3 region, which is a primary target of adenoviral oncoprotein E1A and various nuclear proteins, such as p53, cyclin E, and AP-1, and both are colocalized in the nuclear bodies. CBP/p300 potentiated Lef-mediated transactivation of beta-catenin, and E1A, a potent inhibitor of CBP/p300, repressed its transactivation. Furthermore, overexpression of stable beta-catenin mutant competitively suppressed the p53-dependent pathway. These may be a key mechanism of beta-catenin involved in oncogenic events underlying disruption of tumor suppressor function through CBP/p300.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis*
-
Blotting, Western
-
Cell Line
-
Cell Nucleus / metabolism
-
Cyclin E / metabolism
-
Cytoskeletal Proteins / genetics
-
Cytoskeletal Proteins / metabolism*
-
Cytoskeletal Proteins / physiology
-
DNA-Binding Proteins / metabolism*
-
Fluorescent Antibody Technique
-
Glutathione Transferase / metabolism
-
HeLa Cells
-
Humans
-
In Situ Nick-End Labeling
-
Lymphoid Enhancer-Binding Factor 1
-
Models, Genetic
-
Mutagenesis
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Nuclear Proteins / physiology
-
Plasmids / metabolism
-
Precipitin Tests
-
Protein Binding
-
Protein Structure, Tertiary
-
Recombinant Fusion Proteins / metabolism
-
Trans-Activators / genetics
-
Trans-Activators / metabolism*
-
Trans-Activators / physiology
-
Transcription Factor AP-1 / metabolism
-
Transcription Factors / metabolism*
-
Transcription, Genetic*
-
Transcriptional Activation
-
Tumor Suppressor Protein p53 / metabolism*
-
Up-Regulation
-
beta Catenin
Substances
-
CTNNB1 protein, human
-
Cyclin E
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Lymphoid Enhancer-Binding Factor 1
-
Nuclear Proteins
-
Recombinant Fusion Proteins
-
Trans-Activators
-
Transcription Factor AP-1
-
Transcription Factors
-
Tumor Suppressor Protein p53
-
beta Catenin
-
Glutathione Transferase