[HTML][HTML] Excess β-catenin promotes accumulation of transcriptionally active p53

A Damalas, A Ben-Ze'ev, I Simcha, M Shtutman… - The EMBO …, 1999 - embopress.org
A Damalas, A Ben-Ze'ev, I Simcha, M Shtutman, JFM Leal, J Zhurinsky, B Geiger, M Oren
The EMBO Journal, 1999embopress.org
β-catenin is a multifunctional protein, acting both as a structural component of the cell
adhesion machinery and as a transducer of extracellular signals. Deregulated β-catenin
protein expression, due to mutations in the β-catenin gene itself or in its upstream regulator,
the adenomatous polyposis coli (APC) gene, is prevalent in colorectal cancer and in several
other tumor types, and attests to the potential oncogenic activity of this protein. Increased
expression of β-catenin is an early event in colorectal carcinogenesis, and is usually …
β-catenin is a multifunctional protein, acting both as a structural component of the cell adhesion machinery and as a transducer of extracellular signals. Deregulated β-catenin protein expression, due to mutations in the β-catenin gene itself or in its upstream regulator, the adenomatous polyposis coli (APC) gene, is prevalent in colorectal cancer and in several other tumor types, and attests to the potential oncogenic activity of this protein. Increased expression of β-catenin is an early event in colorectal carcinogenesis, and is usually followed by a later mutational inactivation of the p53 tumor suppressor. To examine whether these two key steps in carcinogenesis are interrelated, we studied the effect of excess β-catenin on p53. We report here that overexpression of β-catenin results in accumulation of p53, apparently through interference with its proteolytic degradation. This effect involves both Mdm2-dependent and-independent p53 degradation pathways, and is accompanied by augmented transcriptional activity of p53 in the affected cells. Increased p53 activity may provide a safeguard against oncogenic deregulation of β-catenin, and thus impose a pressure for mutational inactivation of p53 during the later stages of tumor progression.
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