Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/126538
Title: Beta-catenin cleavage enhances transcriptional activation
Author: Goretsky, Tatiana
Bradford, Emily M.
Ye, Qing
Lamping, Olivia F.
Vanagunas, Tomas
Moyer, Mary Pat
Keller, Patrick C.
Sinh, Preetika
Llovet i Bayer, Josep Maria
Gao, Tianyan
She, Qing-Bai
Li, Linheng
Barrett, Terrence A.
Keywords: Colitis
Càncer colorectal
Inflamació
Colitis
Colorectal cancer
Inflammation
Issue Date: 12-Jan-2018
Publisher: Nature Publishing Group
Abstract: Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat552 in the nucleus of inflamed and cancerous cells. Nuclear chromatin bound localization of LMW pβ-Cat552 was blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not by other protease inhibitors. K48 polyubiquitinated FS and LMW β-catenin were increased by treatment with bortezomib. Overexpressed in vitro double truncated β-catenin increased transcriptional activity, cell proliferation and growth of tumor xenografts compared to FS β-catenin. Serine 552-> alanin substitution abrogated K48 polyubiquitination, β-catenin nuclear translocation and tumor xenograft growth. These data suggest that a novel proteasome-dependent posttranslational modification of β-catenin enhances transcriptional activation. Discovery of this pathway may be helpful in the development of diagnostic and therapeutic tools in colitis and cancer.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41598-017-18421-8
It is part of: Scientific Reports, 2018, vol. 8, num. 1, p. 671
URI: http://hdl.handle.net/2445/126538
Related resource: https://doi.org/10.1038/s41598-017-18421-8
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Medicina)

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