RRC ID 63065
Author Nishimoto A, Takemoto Y, Saito T, Kurazumi H, Tanaka T, Harada E, Shirasawa B, Hamano K.
Title Nuclear β-catenin expression is positively regulated by JAB1 in human colorectal cancer cells.
Journal Biochem Biophys Res Commun
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.
Volume 533(3)
Pages 548-552
Published 2020-12-10
DOI 10.1016/j.bbrc.2020.09.007
PII S0006-291X(20)31745-9
PMID 32977947
MeSH COP9 Signalosome Complex / physiology* Cell Line, Tumor Cell Nucleus / metabolism Colorectal Neoplasms / metabolism* DNA Topoisomerases, Type II / metabolism Humans Intracellular Signaling Peptides and Proteins / physiology* Ki-67 Antigen / metabolism Peptide Hydrolases / physiology* Poly-ADP-Ribose Binding Proteins / metabolism Proto-Oncogene Proteins c-myc / metabolism Transcription Factor 7-Like 2 Protein / metabolism beta Catenin / metabolism*
IF 2.985
Human and Animal Cells CACO-2(RCB0988) CW-2(RCB0778) COLO-320(RCB1193) COLO205(RCB2127) LoVo(RCB1639)