Biochemical and Biophysical Research Communications, Vol.533, No.3, 548-552, 2020
Nuclear beta-catenin expression is positively regulated by JAB1 in human colorectal cancer cells
Wnt/beta-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for beta-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of beta-catenin and its translocation into the nucleus. Nuclear beta-catenin interacts with and coactivates T cell factor4 (TCF4), resulting in beta-catenin/TCF4-dependent transcription. Therefore, nuclear beta-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 beta-catenin, and positively regulates the expression of total beta-catenin in human CRC cells. An another recent study also shows that nuclear beta-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 beta-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear beta-catenin, c-MYC as a beta-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase II alpha in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy. (C) 2020 Published by Elsevier Inc.