| Abstract |
Wnt/β-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for β-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of β-catenin and its translocation into the nucleus. Nuclear β-catenin interacts with and co-activates T cell factor4 (TCF4), resulting in β-catenin/TCF4-dependent transcription. Therefore, nuclear β-catenin has been categorized as the main driving force in the tumorigenesis of CRC. Recent studies reveal that Jun activation domain-binding protein 1 (JAB1) enhances the degradation of seven in absentia homolog-1 (SIAH-1), a putative E3 ubiquitin ligase of β-catenin, and positively regulates the expression of total β-catenin in human CRC cells. An another recent study also shows that nuclear β-catenin is ubiquitinated and degraded by an E3 ubiquitin ligase, tripartite motif-containing protein 33 (TRIM33). However, the regulatory mechanism for the expression of nuclear β-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear β-catenin, c-MYC as a β-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase IIα, in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy.
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